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Reciprocal regulations between miRNAs and HIF-1α in human cancers

  • Wanli Yang
  • Jiaojiao Ma
  • Wei Zhou
  • Bo Cao
  • Xin Zhou
  • Hongwei Zhang
  • Qingchuan Zhao
  • Liu Hong
  • Daiming Fan
Review

Abstract

Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients’ outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs. Evidence shows that miRNAs can be regulated by HIF-1α at transcriptional level. In turn, HIF-1α itself can be modulated by many miRNAs whose alterations have been implicated in tumorigenesis, thus forming a reciprocal regulation network. These findings add a new layer of complexity to our understanding of HIF-1α regulatory networks. Here, we will provide a comprehensive overview of the current advances about the bidirectional interactions between HIF-1α and miRNAs in human cancers. Besides, the review will summarize the roles of miRNAs/HIF-1α crosstalk according to various cellular processes. Finally, the potential values of miRNAs/HIF-1α loops in clinical applications are discussed.

Keywords

miRNAs HIF-1α Cancer Proliferation Apoptosis Metastasis 

Notes

Acknowledgements

This study was supported in part by Grant from the National Natural Scientific Foundation of China (81171923), Grant from the State Key Laboratory of Cancer Biology (CBSKL2014Z13) and Grant from the National Clinical Research Center for Digestive Diseases(2015BAI13B07). It was not supported by any private or public company or organization.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

Supplementary material

18_2018_2941_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 22 kb)

References

  1. 1.
    Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732.  https://doi.org/10.1038/nrc1187 CrossRefPubMedGoogle Scholar
  2. 2.
    Semenza GL (2007) Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE 2007(407):cm8.  https://doi.org/10.1126/stke.4072007cm8 CrossRefPubMedGoogle Scholar
  3. 3.
    Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science (New York, NY) 292(5516):468–472.  https://doi.org/10.1126/science.1059796 CrossRefGoogle Scholar
  4. 4.
    Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda, Md) 19:176–182.  https://doi.org/10.1152/physiol.00001.2004 CrossRefGoogle Scholar
  5. 5.
    Chan DA, Sutphin PD, Yen SE, Giaccia AJ (2005) Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha. Mol Cell Biol 25(15):6415–6426.  https://doi.org/10.1128/mcb.25.15.6415-6426.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    D’Angelo G, Duplan E, Boyer N, Vigne P, Frelin C (2003) Hypoxia up-regulates prolyl hydroxylase activity: a feedback mechanism that limits HIF-1 responses during reoxygenation. J Biol Chem 278(40):38183–38187.  https://doi.org/10.1074/jbc.M302244200 CrossRefPubMedGoogle Scholar
  7. 7.
    Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40(2):294–309.  https://doi.org/10.1016/j.molcel.2010.09.022 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kaelin WG Jr, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30(4):393–402.  https://doi.org/10.1016/j.molcel.2008.04.009 CrossRefPubMedGoogle Scholar
  9. 9.
    Semenza GL (2010) Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29(5):625–634.  https://doi.org/10.1038/onc.2009.441 CrossRefPubMedGoogle Scholar
  10. 10.
    Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L et al (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science (New York, NY) 260(5112):1317–1320CrossRefGoogle Scholar
  11. 11.
    Webb JD, Coleman ML, Pugh CW (2009) Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell Mol Life Sci 66(22):3539–3554.  https://doi.org/10.1007/s00018-009-0147-7 CrossRefPubMedGoogle Scholar
  12. 12.
    Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275(33):25130–25138.  https://doi.org/10.1074/jbc.M001914200 CrossRefPubMedGoogle Scholar
  13. 13.
    Lau KW, Tian YM, Raval RR, Ratcliffe PJ, Pugh CW (2007) Target gene selectivity of hypoxia-inducible factor-alpha in renal cancer cells is conveyed by post-DNA-binding mechanisms. Br J Cancer 96(8):1284–1292.  https://doi.org/10.1038/sj.bjc.6603675 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Nagaraju GP, Bramhachari PV, Raghu G, El-Rayes BF (2015) Hypoxia inducible factor-1alpha: its role in colorectal carcinogenesis and metastasis. Cancer Lett 366(1):11–18.  https://doi.org/10.1016/j.canlet.2015.06.005 CrossRefPubMedGoogle Scholar
  15. 15.
    Haque I, Banerjee S, Mehta S, De A, Majumder M, Mayo MS, Kambhampati S, Campbell DR, Banerjee SK (2011) Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates microRNA-10b via hypoxia-inducible factor-1alpha-TWIST signaling networks in human breast cancer cells. J Biol Chem 286(50):43475–43485.  https://doi.org/10.1074/jbc.M111.284158 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chai ZT, Kong J, Zhu XD, Zhang YY, Lu L, Zhou JM, Wang LR, Zhang KZ, Zhang QB, Ao JY, Wang M, Wu WZ, Wang L, Tang ZY, Sun HC (2013) MicroRNA-26a inhibits angiogenesis by down-regulating VEGFA through the PIK3C2alpha/Akt/HIF-1alpha pathway in hepatocellular carcinoma. PLoS One 8(10):e77957.  https://doi.org/10.1371/journal.pone.0077957 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhang C, Tian W, Meng L, Qu L, Shou C (2016) PRL-3 promotes gastric cancer migration and invasion through a NF-kappaB-HIF-1alpha-miR-210 axis. J Mol Med (Berlin, Germany) 94(4):401–415.  https://doi.org/10.1007/s00109-015-1350-7 CrossRefGoogle Scholar
  18. 18.
    Brahimi-Horn MC, Ben-Hail D, Ilie M, Gounon P, Rouleau M, Hofman V, Doyen J, Mari B, Shoshan-Barmatz V, Hofman P, Pouyssegur J, Mazure NM (2012) Expression of a truncated active form of VDAC1 in lung cancer associates with hypoxic cell survival and correlates with progression to chemotherapy resistance. Can Res 72(8):2140–2150.  https://doi.org/10.1158/0008-5472.can-11-3940 CrossRefGoogle Scholar
  19. 19.
    Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Can Res 59(22):5830–5835Google Scholar
  20. 20.
    Shen XH, Qi P, Du X (2015) Long non-coding RNAs in cancer invasion and metastasis. Mod Pathol 28(1):4–13.  https://doi.org/10.1038/modpathol.2014.75 CrossRefPubMedGoogle Scholar
  21. 21.
    Munipalle PC, Viswanath YK, Davis PA, Scoones D (2011) Prognostic value of hypoxia inducible factor 1alpha in esophageal squamous cell carcinoma. Dis Esophagus 24(3):177–181.  https://doi.org/10.1111/j.1442-2050.2010.01122.x CrossRefPubMedGoogle Scholar
  22. 22.
    Marton I, Knezevic F, Ramic S, Milosevic M, Tomas D (2012) Immunohistochemical expression and prognostic significance of HIF-1alpha and VEGF-C in neuroendocrine breast cancer. Anticancer Res 32(12):5227–5232PubMedGoogle Scholar
  23. 23.
    Shen W, Li HL, Liu L, Cheng JX (2017) Expression levels of PTEN, HIF-1alpha, and VEGF as prognostic factors in ovarian cancer. Eur Rev Med Pharmacol Sci 21(11):2596–2603PubMedGoogle Scholar
  24. 24.
    Gong L, Zhang W, Zhou J, Lu J, Xiong H, Shi X, Chen J (2013) Prognostic value of HIFs expression in head and neck cancer: a systematic review. PLoS One 8(9):e75094.  https://doi.org/10.1371/journal.pone.0075094 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ben Lassoued A, Beaufils N, Dales JP, Gabert J (2013) Hypoxia-inducible factor-1alpha as prognostic marker. Expert Opin Med Diagn 7(1):53–70.  https://doi.org/10.1517/17530059.2012.719022 CrossRefPubMedGoogle Scholar
  26. 26.
    Keremu A, Aini A, Maimaitirexiati Y, Liang Z, Aila P, Xierela P, Tusun A, Moming H, Yusufu A (2017) Overcoming cisplatin resistance in osteosarcoma through the miR-199a-modulated inhibition of HIF-1alpha. Biosci Rep.  https://doi.org/10.1042/bsr20170080 CrossRefPubMedGoogle Scholar
  27. 27.
    Gao Y, Feng B, Lu L, Han S, Chu X, Chen L, Wang R (2017) MiRNAs and E2F3: a complex network of reciprocal regulations in human cancers. Oncotarget.  https://doi.org/10.18632/oncotarget.17364 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Xu W, Zhang Z, Zou K, Cheng Y, Yang M, Chen H, Wang H, Zhao J, Chen P, He L, Chen X, Geng L, Gong S (2017) MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis. Cell Death Dis 8(5):e2761.  https://doi.org/10.1038/cddis.2017.60 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Li B, He L, Zuo D, He W, Wang Y, Zhang Y, Liu W, Yuan Y (2017) Mutual regulation of MiR-199a-5p and HIF-1alpha modulates the warburg effect in hepatocellular carcinoma. J Cancer 8(6):940–949.  https://doi.org/10.7150/jca.17496 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Liu N, Xia WY, Liu SS, Chen HY, Sun L, Liu MY, Li LF, Lu HM, Fu YJ, Wang P, Wu H, Gao JX (2016) MicroRNA-101 targets von Hippel-Lindau tumor suppressor (VHL) to induce HIF1alpha mediated apoptosis and cell cycle arrest in normoxia condition. Sci Rep 6:20489.  https://doi.org/10.1038/srep20489 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Dang K, Myers KA (2015) The role of hypoxia-induced miR-210 in cancer progression. Int J Mol Sci 16(3):6353–6372.  https://doi.org/10.3390/ijms16036353 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Yang Q, Zhang RW, Sui PC, He HT, Ding L (2015) Dysregulation of non-coding RNAs in gastric cancer. World J Gastroenterol 21(39):10956–10981.  https://doi.org/10.3748/wjg.v21.i39.10956 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Li M, Wang Y, Song Y, Bu R, Yin B, Fei X, Guo Q, Wu B (2015) MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (Review). Oncol Rep 33(4):1571–1578.  https://doi.org/10.3892/or.2015.3799 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ang C, O’Reilly EM, Abou-Alfa GK (2011) MicroRNA, hypoxic stress and hepatocellular carcinoma: future directions. J Gastroenterol Hepatol 26(11):1586–1588.  https://doi.org/10.1111/j.1440-1746.2011.06903.x CrossRefPubMedGoogle Scholar
  35. 35.
    Ling H, Fabbri M, Calin GA (2013) MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 12(11):847–865.  https://doi.org/10.1038/nrd4140 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Schmitz SU, Grote P, Herrmann BG (2016) Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci 73(13):2491–2509.  https://doi.org/10.1007/s00018-016-2174-5 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Suzuki H, Maruyama R, Yamamoto E, Niinuma T, Kai M (2016) Relationship between noncoding RNA dysregulation and epigenetic mechanisms in cancer. Adv Exp Med Biol 927:109–135.  https://doi.org/10.1007/978-981-10-1498-7_4 CrossRefPubMedGoogle Scholar
  38. 38.
    Yang Z, Guo X, Li G, Shi Y, Li L (2016) Long noncoding RNAs as potential biomarkers in gastric cancer: opportunities and challenges. Cancer Lett 371(1):62–70.  https://doi.org/10.1016/j.canlet.2015.11.011 CrossRefPubMedGoogle Scholar
  39. 39.
    Dong L, Qi P, Xu MD, Ni SJ, Huang D, Xu QH, Weng WW, Tan C, Sheng WQ, Zhou XY, Du X (2015) Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int J Cancer 137(5):1128–1135.  https://doi.org/10.1002/ijc.29484 CrossRefPubMedGoogle Scholar
  40. 40.
    Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, Mo YY (2014) Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis 5:e1008.  https://doi.org/10.1038/cddis.2013.541 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Li T, Yang XD, Ye CX, Shen ZL, Yang Y, Wang B, Guo P, Gao ZD, Ye YJ, Jiang KW, Wang S (2017) Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene. Cell Cycle (Georgetown, Tex) 16(2):224–231.  https://doi.org/10.1080/15384101.2016.1261768 CrossRefGoogle Scholar
  42. 42.
    Shih JW, Kung HJ (2017) Long non-coding RNA and tumor hypoxia: new players ushered toward an old arena. J Biomed Sci 24(1):53.  https://doi.org/10.1186/s12929-017-0358-4 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wang P, Ning S, Zhang Y, Li R, Ye J, Zhao Z, Zhi H, Wang T, Guo Z, Li X (2015) Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer. Nucleic Acids Res 43(7):3478–3489.  https://doi.org/10.1093/nar/gkv233 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Zhong J, Huang R, Su Z, Zhang M, Xu M, Gong J, Chen N, Zeng H, Chen X, Zhou Q (2017) Downregulation of miR-199a-5p promotes prostate adeno-carcinoma progression through loss of its inhibition of HIF-1alpha. Oncotarget.  https://doi.org/10.18632/oncotarget.18315 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Shang W, Chen X, Nie L, Xu M, Chen N, Zeng H, Zhou Q (2013) MiR199b suppresses expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in prostate cancer cells. Int J Mol Sci 14(4):8422–8436.  https://doi.org/10.3390/ijms14048422 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Ye H, Pang L, Wu Q, Zhu Y, Guo C, Deng Y, Zheng X (2015) A critical role of mir-199a in the cell biological behaviors of colorectal cancer. Diagn Pathol 10:65.  https://doi.org/10.1186/s13000-015-0260-x CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Joshi HP, Subramanian IV, Schnettler EK, Ghosh G, Rupaimoole R, Evans C, Saluja M, Jing Y, Cristina I, Roy S, Zeng Y, Shah VH, Sood AK, Ramakrishnan S (2014) Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc Natl Acad Sci USA 111(14):5331–5336.  https://doi.org/10.1073/pnas.1317242111 CrossRefPubMedGoogle Scholar
  48. 48.
    Obernosterer G, Leuschner PJ, Alenius M, Martinez J (2006) Post-transcriptional regulation of microRNA expression. RNA (New York, NY) 12(7):1161–1167.  https://doi.org/10.1261/rna.2322506 CrossRefGoogle Scholar
  49. 49.
    Weber MJ (2005) New human and mouse microRNA genes found by homology search. FEBS J 272(1):59–73.  https://doi.org/10.1111/j.1432-1033.2004.04389.x CrossRefPubMedGoogle Scholar
  50. 50.
    Jin Y, Chen D, Cabay RJ, Wang A, Crowe DL, Zhou X (2013) Role of microRNA-138 as a potential tumor suppressor in head and neck squamous cell carcinoma. Int Rev Cell Mol Biol 303:357–385.  https://doi.org/10.1016/b978-0-12-407697-6.00009-x CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Yeh YM, Chuang CM, Chao KC, Wang LH (2013) MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1alpha. Int J Cancer 133(4):867–878.  https://doi.org/10.1002/ijc.28086 CrossRefPubMedGoogle Scholar
  52. 52.
    Cai Q, Wang Z, Wang S, Weng M, Zhou D, Li C, Wang J, Chen E, Quan Z (2017) Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial–mesenchymal transition by regulating HIF-1alpha via miR-138. Open Biol.  https://doi.org/10.1098/rsob.160247 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J, Hong B (2011) MiR-138 suppresses expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev 12(5):1307–1311PubMedGoogle Scholar
  54. 54.
    Chen Y, Zhang Z, Luo C, Chen Z, Zhou J (2016) MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1alpha-mediated glycolysis. Oncol Rep 36(1):471–479.  https://doi.org/10.3892/or.2016.4824 CrossRefPubMedGoogle Scholar
  55. 55.
    Li X, Wu Y, Liu A, Tang X (2016) Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1alpha feedback regulatory loop. Tumour Biol 37(11):14733–14743.  https://doi.org/10.1007/s13277-016-5348-8 CrossRefPubMedGoogle Scholar
  56. 56.
    Wu F, Huang W, Wang X (2015) microRNA-18a regulates gastric carcinoma cell apoptosis and invasion by suppressing hypoxia-inducible factor-1alpha expression. Exp Ther Med 10(2):717–722.  https://doi.org/10.3892/etm.2015.2546 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Han C, Shen JK, Hornicek FJ, Kan Q (1860) Duan Z (2017) Regulation of microRNA-1 (miR-1) expression in human cancer. Biochem Biophys Acta 2:227–232.  https://doi.org/10.1016/j.bbagrm.2016.12.004 CrossRefGoogle Scholar
  58. 58.
    Lu Y, Ji N, Wei W, Sun W, Gong X, Wang X (2017) MiR-142 modulates human pancreatic cancer proliferation and invasion by targeting hypoxia-inducible factor 1 (HIF-1alpha) in the tumor microenvironments. Biol Open 6(2):252–259.  https://doi.org/10.1242/bio.021774 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Liu L, Wang Y, Bai R, Yang K, Tian Z (2016) MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1alpha regulation. Oncogenesis 5:e224.  https://doi.org/10.1038/oncsis.2016.35 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Zhang R, Zhao J, Xu J, Wang J, Jia J (2016) miR-526b-3p functions as a tumor suppressor in colon cancer by regulating HIF-1alpha. Am J Transl Res 8(6):2783–2789PubMedPubMedCentralGoogle Scholar
  61. 61.
    Yamakuchi M, Yagi S, Ito T, Lowenstein CJ (2011) MicroRNA-22 regulates hypoxia signaling in colon cancer cells. PLoS One 6(5):e20291.  https://doi.org/10.1371/journal.pone.0020291 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wu Z, Cai X, Huang C, Xu J, Liu A (2016) miR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1alpha. Oncol Rep 35(3):1696–1702.  https://doi.org/10.3892/or.2015.4529 CrossRefPubMedGoogle Scholar
  63. 63.
    Cheng CW, Chen PM, Hsieh YH, Weng CC, Chang CW, Yao CC, Hu LY, Wu PE, Shen CY (2015) Foxo3a-mediated overexpression of microRNA-622 suppresses tumor metastasis by repressing hypoxia-inducible factor-1alpha in ERK-responsive lung cancer. Oncotarget 6(42):44222–44238.  https://doi.org/10.18632/oncotarget.5826 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM, Yu SL, Chen JS, Chang KJ, Jee SH, Tan CT, Lin MT, Kuo ML (2010) MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Can Res 70(7):2675–2685.  https://doi.org/10.1158/0008-5472.can-09-2448 CrossRefGoogle Scholar
  65. 65.
    Ambade A, Satishchandran A, Szabo G (2016) Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1alpha activation. Sci Rep 6:21340.  https://doi.org/10.1038/srep21340 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Takahashi K, Yan IK, Haga H, Patel T (2014) Modulation of hypoxia-signaling pathways by extracellular linc-RoR. J Cell Sci 127(Pt 7):1585–1594.  https://doi.org/10.1242/jcs.141069 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kulshreshtha R, Ferracin M, Negrini M, Calin GA, Davuluri RV, Ivan M (2007) Regulation of microRNA expression: the hypoxic component. Cell Cycle (Georgetown, Tex) 6(12):1426–1431CrossRefGoogle Scholar
  68. 68.
    Voellenkle C, Rooij J, Guffanti A, Brini E, Fasanaro P, Isaia E, Croft L, David M, Capogrossi MC, Moles A, Felsani A, Martelli F (2012) Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA (New York, NY) 18(3):472–484.  https://doi.org/10.1261/rna.027615.111 CrossRefGoogle Scholar
  69. 69.
    Gee HE, Ivan C, Calin GA, Ivan M (2014) HypoxamiRs and cancer: from biology to targeted therapy. Antioxid Redox Signal 21(8):1220–1238.  https://doi.org/10.1089/ars.2013.5639 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Zhang L, Sun ZJ, Bian Y, Kulkarni AB (2013) MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett 331(2):230–238.  https://doi.org/10.1016/j.canlet.2013.01.003 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Xie Z, Cao L, Zhang J (2013) miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1alpha expression in human ovarian cancer cells. Oncol Lett 6(3):795–800.  https://doi.org/10.3892/ol.2013.1432 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Han M, Wang Y, Liu M, Bi X, Bao J, Zeng N, Zhu Z, Mo Z, Wu C, Chen X (2012) MiR-21 regulates epithelial–mesenchymal transition phenotype and hypoxia-inducible factor-1alpha expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci 103(6):1058–1064.  https://doi.org/10.1111/j.1349-7006.2012.02281.x CrossRefPubMedGoogle Scholar
  73. 73.
    Yang W, Ma J, Zhou W, Zhou X, Cao B, Fan D, Hong L (2017) Biological implications and clinical value of mir-210 in gastrointestinal cancer. Expert Rev Gastroenterol Hepatol 11(6):539–548.  https://doi.org/10.1080/17474124.2017.1309281 CrossRefPubMedGoogle Scholar
  74. 74.
    Ren CX, Leng RX, Fan YG, Pan HF, Wu CH, Ye DQ (2016) MicroRNA-210 and its theranostic potential. Expert Opin Ther Targets 20(11):1325–1338.  https://doi.org/10.1080/14728222.2016.1206890 CrossRefPubMedGoogle Scholar
  75. 75.
    Wang Z, Deng M, Liu Z, Wu S (2017) Hypoxia-induced miR-210 promoter demethylation enhances proliferation, autophagy and angiogenesis of schwannoma cells. Oncol Rep 37(5):3010–3018.  https://doi.org/10.3892/or.2017.5511 CrossRefPubMedGoogle Scholar
  76. 76.
    Liu T, Zhao L, Chen W, Li Z, Hou H, Ding L, Li X (2014) Inactivation of von Hippel-Lindau increases ovarian cancer cell aggressiveness through the HIF1alpha/miR-210/VMP1 signaling pathway. Int J Mol Med 33(5):1236–1242.  https://doi.org/10.3892/ijmm.2014.1661 CrossRefPubMedGoogle Scholar
  77. 77.
    Li L, Huang K, You Y, Fu X, Hu L, Song L, Meng Y (2014) Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis. Int J Oncol 44(6):2111–2120.  https://doi.org/10.3892/ijo.2014.2368 CrossRefPubMedGoogle Scholar
  78. 78.
    Chen KC, Liao YC, Wang JY, Lin YC, Chen CH, Juo SH (2015) Oxidized low-density lipoprotein is a common risk factor for cardiovascular diseases and gastroenterological cancers via epigenomical regulation of microRNA-210. Oncotarget 6(27):24105–24118.  https://doi.org/10.18632/oncotarget.4152 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Saenz-de-Santa-Maria I, Bernardo-Castineira C, Secades P, Bernaldo-de-Quiros S, Rodrigo JP, Astudillo A, Chiara MD (2017) Clinically relevant HIF-1alpha-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation. Oncotarget 8(8):13730–13746.  https://doi.org/10.18632/oncotarget.14629 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Merlo A, Bernardo-Castineira C, Saenz-de-Santa-Maria I, Pitiot AS, Balbin M, Astudillo A, Valdes N, Scola B, Del Toro R, Mendez-Ferrer S, Piruat JI, Suarez C, Chiara MD (2017) Role of VHL, HIF1A and SDH on the expression of miR-210: implications for tumoral pseudo-hypoxic fate. Oncotarget 8(4):6700–6717.  https://doi.org/10.18632/oncotarget.14265 CrossRefPubMedGoogle Scholar
  81. 81.
    Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M, Moriyama M (2011) Overexpression of miR-210, a downstream target of HIF1alpha, causes centrosome amplification in renal carcinoma cells. J Pathol 224(2):280–288.  https://doi.org/10.1002/path.2860 CrossRefPubMedGoogle Scholar
  82. 82.
    Kai AK, Chan LK, Lo RC, Lee JM, Wong CC, Wong JC, Ng IO (2016) Down-regulation of TIMP2 by HIF-1alpha/miR-210/HIF-3alpha regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma. Hepatology (Baltimore, MD) 64(2):473–487.  https://doi.org/10.1002/hep.28577 CrossRefGoogle Scholar
  83. 83.
    Sun Y, Xing X, Liu Q, Wang Z, Xin Y, Zhang P, Hu C, Liu Y (2015) Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1alpha/miR-210/Bcl-2 pathway in colon cancer cells. Int J Oncol 46(2):750–756.  https://doi.org/10.3892/ijo.2014.2745 CrossRefPubMedGoogle Scholar
  84. 84.
    Yu P, Fan S, Huang L, Yang L, Du Y (2015) MIR210 as a potential molecular target to block invasion and metastasis of gastric cancer. Med Hypotheses 84(3):209–212.  https://doi.org/10.1016/j.mehy.2014.12.024 CrossRefPubMedGoogle Scholar
  85. 85.
    Chen WY, Liu WJ, Zhao YP, Zhou L, Zhang TP, Chen G, Shu H (2012) Induction, modulation and potential targets of miR-210 in pancreatic cancer cells. Hepatobil Pancreat Dis Int 11(3):319–324CrossRefGoogle Scholar
  86. 86.
    Li CL, Zhou XL, Wang YD, Jing SW, Yang CR, Sun GG, Liu Q, Cheng YJ, Wang L (2014) miR-210 regulates esophageal cancer cell proliferation by inducing G(2)/M phase cell cycle arrest through targeting PLK1. Mol Med Rep 10(4):2099–2104.  https://doi.org/10.3892/mmr.2014.2416 CrossRefPubMedGoogle Scholar
  87. 87.
    Song L, Liu S, Zhang L, Yao H, Gao F, Xu D, Li Q (2016) MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1alpha feedback loop and the Akt-mTOR signaling pathway. Tumour Biol 37(9):12161–12168.  https://doi.org/10.1007/s13277-016-5073-3 CrossRefPubMedGoogle Scholar
  88. 88.
    Li L, Li C, Wang S, Wang Z, Jiang J, Wang W, Li X, Chen J, Liu K, Li C, Zhu G (2016) Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype. Can Res 76(7):1770–1780.  https://doi.org/10.1158/0008-5472.can-15-1625 CrossRefGoogle Scholar
  89. 89.
    Mace TA, Collins AL, Wojcik SE, Croce CM, Lesinski GB, Bloomston M (2013) Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res 184(2):855–860.  https://doi.org/10.1016/j.jss.2013.04.061 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Zhao J, Qiao CR, Ding Z, Sheng YL, Li XN, Yang Y, Zhu DY, Zhang CY, Liu DL, Wu K, Zhao S (2017) A novel pathway in NSCLC cells: miR191, targeting NFIA, is induced by chronic hypoxia, and promotes cell proliferation and migration. Mol Med Rep 15(3):1319–1325.  https://doi.org/10.3892/mmr.2017.6100 CrossRefPubMedGoogle Scholar
  91. 91.
    He C, Wang L, Zhang J, Xu H (2017) Hypoxia-inducible microRNA-224 promotes the cell growth, migration and invasion by directly targeting RASSF8 in gastric cancer. Mol Cancer 16(1):35.  https://doi.org/10.1186/s12943-017-0603-1 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Ge X, Liu X, Lin F, Li P, Liu K, Geng R, Dai C, Lin Y, Tang W, Wu Z, Chang J, Lu J, Li J (2016) MicroRNA-421 regulated by HIF-1alpha promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer. Oncotarget 7(17):24466–24482.  https://doi.org/10.18632/oncotarget.8228 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Zhao Q, Li Y, Tan BB, Fan LQ, Yang PG, Tian Y (2015) HIF-1alpha induces multidrug resistance in gastric cancer cells by inducing MiR-27a. PLoS One 10(8):e0132746.  https://doi.org/10.1371/journal.pone.0132746 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Ayremlou N, Mozdarani H, Mowla SJ, Delavari A (2015) Increased levels of serum and tissue miR-107 in human gastric cancer: correlation with tumor hypoxia. Cancer Biomark Sect A Dis Mark 15(6):851–860.  https://doi.org/10.3233/cbm-150529 CrossRefGoogle Scholar
  95. 95.
    Seok JK, Lee SH, Kim MJ, Lee YM (2014) MicroRNA-382 induced by HIF-1alpha is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucleic Acids Res 42(12):8062–8072.  https://doi.org/10.1093/nar/gku515 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Wang XJ, Zhang DL, Fu C, Wei BZ, Li GJ (2016) MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1alpha feedback loop. Eur Rev Med Pharmacol Sci 20(10):2020–2027PubMedGoogle Scholar
  97. 97.
    Mao G, Liu Y, Fang X, Liu Y, Fang L, Lin L, Liu X, Wang N (2015) Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer. Angiogenesis 18(3):373–382.  https://doi.org/10.1007/s10456-015-9474-5 CrossRefPubMedGoogle Scholar
  98. 98.
    Blick C, Ramachandran A, McCormick R, Wigfield S, Cranston D, Catto J, Harris AL (2015) Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis. Br J Cancer 113(4):634–644.  https://doi.org/10.1038/bjc.2015.203 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Yuan Q, Gao W, Liu B, Ye W (2014) Upregulation of miR-184 enhances the malignant biological behavior of human glioma cell line A172 by targeting FIH-1. Cell Physiol Biochem 34(4):1125–1136.  https://doi.org/10.1159/000366326 CrossRefPubMedGoogle Scholar
  100. 100.
    Gits CM, van Kuijk PF, de Rijck JC, Muskens N, Jonkers MB, van Wilfred IF, Mathijssen RH, Verweij J, Sleijfer S, Wiemer EA (2014) MicroRNA response to hypoxic stress in soft tissue sarcoma cells: microRNA mediated regulation of HIF3alpha. BMC Cancer 14:429.  https://doi.org/10.1186/1471-2407-14-429 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Zhu S, He C, Deng S, Li X, Cui S, Zeng Z, Liu M, Zhao S, Chen J, Jin Y, Chen H, Deng S, Liu Y, Wang C, Zhao G (2016) MiR-548an, transcriptionally downregulated by HIF1alpha/HDAC1, suppresses tumorigenesis of pancreatic cancer by targeting vimentin expression. Mol Cancer Ther 15(9):2209–2219.  https://doi.org/10.1158/1535-7163.mct-15-0877 CrossRefPubMedGoogle Scholar
  102. 102.
    He M, Wang QY, Yin QQ, Tang J, Lu Y, Zhou CX, Duan CW, Hong DL, Tanaka T, Chen GQ, Zhao Q (2013) HIF-1alpha downregulates miR-17/20a directly targeting p21 and STAT3: a role in myeloid leukemic cell differentiation. Cell Death Differ 20(3):408–418.  https://doi.org/10.1038/cdd.2012.130 CrossRefPubMedGoogle Scholar
  103. 103.
    Guo XF, Wang AY, Liu J (2016) HIFs-MiR-33a-Twsit1 axis can regulate invasiveness of hepatocellular cancer cells. Eur Rev Med Pharmacol Sci 20(14):3011–3016PubMedGoogle Scholar
  104. 104.
    Cao P, Deng Z, Wan M, Huang W, Cramer SD, Xu J, Lei M, Sui G (2010) MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1alpha/HIF-1beta. Mol Cancer 9:108.  https://doi.org/10.1186/1476-4598-9-108 CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Li H, Rokavec M, Jiang L, Horst D, Hermeking H (2017) Antagonistic effects of p53 and HIF1A on microRNA-34a regulation of PPP1R11 and STAT3 and hypoxia-induced epithelial to mesenchymal transition in colorectal cancer cells. Gastroenterology 153(2):505–520.  https://doi.org/10.1053/j.gastro.2017.04.017 CrossRefPubMedGoogle Scholar
  106. 106.
    Wang X, Ren H, Zhao T, Ma W, Dong J, Zhang S, Xin W, Yang S, Jia L, Hao J (2016) Single nucleotide polymorphism in the microRNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes. Oncotarget 7(12):13717–13729.  https://doi.org/10.18632/oncotarget.7263 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Lo Dico A, Costa V, Martelli C, Diceglie C, Rajata F, Rizzo A, Mancone C, Tripodi M, Ottobrini L, Alessandro R, Conigliaro A (2016) MiR675-5p acts on HIF-1alpha to sustain hypoxic responses: a new therapeutic strategy for glioma. Theranostics 6(8):1105–1118.  https://doi.org/10.7150/thno.14700 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H, Takahashi T (2008) Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Can Res 68(14):5540–5545.  https://doi.org/10.1158/0008-5472.can-07-6460 CrossRefGoogle Scholar
  109. 109.
    Lei Z, Li B, Yang Z, Fang H, Zhang GM, Feng ZH, Huang B (2009) Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One 4(10):e7629.  https://doi.org/10.1371/journal.pone.0007629 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Cascio S, D’Andrea A, Ferla R, Surmacz E, Gulotta E, Amodeo V, Bazan V, Gebbia N, Russo A (2010) miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol 224(1):242–249.  https://doi.org/10.1002/jcp.22126 CrossRefPubMedGoogle Scholar
  111. 111.
    Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, Mendell JT, Huso D, Lowenstein CJ (2010) P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci USA 107(14):6334–6339.  https://doi.org/10.1073/pnas.0911082107 CrossRefPubMedGoogle Scholar
  112. 112.
    Bruning U, Cerone L, Neufeld Z, Fitzpatrick SF, Cheong A, Scholz CC, Simpson DA, Leonard MO, Tambuwala MM, Cummins EP, Taylor CT (2011) MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol 31(19):4087–4096.  https://doi.org/10.1128/mcb.01276-10 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y (2010) Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. J Clin Investig 120(11):4141–4154CrossRefGoogle Scholar
  114. 114.
    Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, Ramakrishnan S (2010) Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J Clin Invest 120(11):4141–4154.  https://doi.org/10.1172/jci42980 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Williams GH, Stoeber K (2012) The cell cycle and cancer. J Pathol 226(2):352–364.  https://doi.org/10.1002/path.3022 CrossRefPubMedGoogle Scholar
  116. 116.
    Yang X, Lei S, Long J, Liu X, Wu Q (2016) MicroRNA-199a-5p inhibits tumor proliferation in melanoma by mediating HIF-1alpha. Mol Med Rep 13(6):5241–5247.  https://doi.org/10.3892/mmr.2016.5202 CrossRefPubMedGoogle Scholar
  117. 117.
    Shan Y, Li X, You B, Shi S, Zhang Q, You Y (2015) MicroRNA-338 inhibits migration and proliferation by targeting hypoxia-induced factor 1alpha in nasopharyngeal carcinoma. Oncol Rep 34(4):1943–1952.  https://doi.org/10.3892/or.2015.4195 CrossRefPubMedGoogle Scholar
  118. 118.
    Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G (2011) MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 286(1):420–428.  https://doi.org/10.1074/jbc.M110.170852 CrossRefPubMedGoogle Scholar
  119. 119.
    Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516.  https://doi.org/10.1080/01926230701320337 CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N (2014) Apoptosis and molecular targeting therapy in cancer. Biomed Res Int 2014:150845.  https://doi.org/10.1155/2014/150845 CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Xu XD, Shao SX, Jiang HP, Cao YW, Wang YH, Yang XC, Wang YL, Wang XS, Niu HT (2015) Warburg effect or reverse Warburg effect? A review of cancer metabolism. Oncol Res Treat 38(3):117–122.  https://doi.org/10.1159/000375435 CrossRefPubMedGoogle Scholar
  122. 122.
    Puissegur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouyssegur J, Gounon P, Hofman P, Barbry P, Mari B (2011) miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ 18(3):465–478.  https://doi.org/10.1038/cdd.2010.119 CrossRefPubMedGoogle Scholar
  123. 123.
    Chen Z, Li Y, Zhang H, Huang P, Luthra R (2010) Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29(30):4362–4368.  https://doi.org/10.1038/onc.2010.193 CrossRefPubMedGoogle Scholar
  124. 124.
    Li JY, Zhang Y, Zhang WH, Jia S, Kang Y, Zhu XY (2012) Differential distribution of miR-20a and miR-20b may underly metastatic heterogeneity of breast cancers. Asian Pac J Cancer Prev 13(5):1901–1906CrossRefGoogle Scholar
  125. 125.
    Giordano G, Febbraro A, Venditti M, Campidoglio S, Olivieri N, Raieta K, Parcesepe P, Imbriani GC, Remo A, Pancione M (2014) Targeting angiogenesis and tumor microenvironment in metastatic colorectal cancer: role of aflibercept. Gastroenterol Res Pract 2014:526178.  https://doi.org/10.1155/2014/526178 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438(7070):932–936.  https://doi.org/10.1038/nature04478 CrossRefPubMedGoogle Scholar
  127. 127.
    Alaiti MA, Ishikawa M, Masuda H, Simon DI, Jain MK, Asahara T, Costa MA (2012) Up-regulation of miR-210 by vascular endothelial growth factor in ex vivo expanded CD34 + cells enhances cell-mediated angiogenesis. J Cell Mol Med 16(10):2413–2421.  https://doi.org/10.1111/j.1582-4934.2012.01557.x CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Yasuda H (2008) Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer. Nitric Oxide 19(2):205–216.  https://doi.org/10.1016/j.niox.2008.04.026 CrossRefPubMedGoogle Scholar
  129. 129.
    Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Can Res 62(12):3387–3394Google Scholar
  130. 130.
    Comerford KM, Cummins EP, Taylor CT (2004) c-Jun NH2-terminal kinase activation contributes to hypoxia-inducible factor 1alpha-dependent P-glycoprotein expression in hypoxia. Can Res 64(24):9057–9061.  https://doi.org/10.1158/0008-5472.can-04-1919 CrossRefGoogle Scholar
  131. 131.
    Moeller BJ, Dewhirst MW (2006) HIF-1 and tumour radiosensitivity. Br J Cancer 95(1):1–5.  https://doi.org/10.1038/sj.bjc.6603201 CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Tafsiri E, Darbouy M, Shadmehr MB, Cho WC, Karimipoor M (2016) Abberant expression of oncogenic and tumor-suppressive microRNAs and their target genes in human adenocarcinoma alveolar basal epithelial cells. J Cancer Res Ther 12(1):395–400.  https://doi.org/10.4103/0973-1482.148673 CrossRefPubMedGoogle Scholar
  133. 133.
    Hwang HW, Baxter LL, Loftus SK, Cronin JC, Trivedi NS, Borate B, Pavan WJ (2014) Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A. Pigment Cell Melanoma Res 27(5):777–787.  https://doi.org/10.1111/pcmr.12255 CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Ke HL, Li WM, Lin HH, Hsu WC, Hsu YL, Chang LL, Huang CN, Li CC, Chang HP, Yeh HC, Li CF, Wu WJ (2017) Hypoxia-regulated MicroRNA-210 overexpression is associated with tumor development and progression in upper tract urothelial carcinoma. Int J Med Sci 14(6):578–584.  https://doi.org/10.7150/ijms.15699 CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J (2008) hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14(5):1340–1348.  https://doi.org/10.1158/1078-0432.ccr-07-1755 CrossRefPubMedGoogle Scholar
  136. 136.
    Cheng HH, Mitchell PS, Kroh EM, Dowell AE, Chery L, Siddiqui J, Nelson PS, Vessella RL, Knudsen BS, Chinnaiyan AM, Pienta KJ, Morrissey C, Tewari M (2013) Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One 8(7):e69239.  https://doi.org/10.1371/journal.pone.0069239 CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Liu K, Yao H, Lei S, Xiong L, Qi H, Qian K, Liu J, Wang P, Zhao H (2017) The miR-124-p63 feedback loop modulates colorectal cancer growth. Oncotarget 8(17):29101–29115.  https://doi.org/10.18632/oncotarget.16248 CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Gao Y, Chen L, Song H, Chen Y, Wang R, Feng B (2016) A double-negative feedback loop between E2F3b and miR-200b regulates docetaxel chemosensitivity of human lung adenocarcinoma cells. Oncotarget 7(19):27613–27626.  https://doi.org/10.18632/oncotarget.8376 CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Zhang Y, Shen WL, Shi ML, Zhang LZ, Zhang Z, Li P, Xing LY, Luo FY, Sun Q, Zheng XF, Yang X, Zhao ZH (2015) Involvement of aberrant miR-139/Jun feedback loop in human gastric cancer. Biochem Biophys Acta 1853 2:481–488.  https://doi.org/10.1016/j.bbamcr.2014.12.002 CrossRefGoogle Scholar
  140. 140.
    Lin CC, Jiang W, Mitra R, Cheng F, Yu H, Zhao Z (2015) Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers. Sci Rep 5:12063.  https://doi.org/10.1038/srep12063 CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Moes M, Le Bechec A, Crespo I, Laurini C, Halavatyi A, Vetter G, Del Sol A, Friederich E (2012) A novel network integrating a miRNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition. PLoS One 7(4):e35440.  https://doi.org/10.1371/journal.pone.0035440 CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Chiang CH, Chu PY, Hou MF, Hung WC (2016) MiR-182 promotes proliferation and invasion and elevates the HIF-1alpha-VEGF-A axis in breast cancer cells by targeting FBXW7. Am J Cancer Res 6(8):1785–1798PubMedPubMedCentralGoogle Scholar
  143. 143.
    Irlam-Jones JJ, Eustace A, Denley H, Choudhury A, Harris AL, Hoskin PJ, West CM (2016) Expression of miR-210 in relation to other measures of hypoxia and prediction of benefit from hypoxia modification in patients with bladder cancer. Br J Cancer 115(5):571–578.  https://doi.org/10.1038/bjc.2016.218 CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Zhao D, Tu Y, Wan L, Bu L, Huang T, Sun X, Wang K, Shen B (2013) In vivo monitoring of angiogenesis inhibition via down-regulation of mir-21 in a VEGFR2-luc murine breast cancer model using bioluminescent imaging. PLoS One 8(8):e71472.  https://doi.org/10.1371/journal.pone.0071472 CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Yang W, Wei J, Guo T, Shen Y, Liu F (2014) Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and radioresistance. Exp Cell Res 326(1):22–35.  https://doi.org/10.1016/j.yexcr.2014.05.022 CrossRefPubMedGoogle Scholar
  146. 146.
    Lytle JR, Yario TA, Steitz JA (2007) Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci USA 104(23):9667–9672.  https://doi.org/10.1073/pnas.0703820104 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Wanli Yang
    • 1
  • Jiaojiao Ma
    • 1
  • Wei Zhou
    • 1
  • Bo Cao
    • 2
  • Xin Zhou
    • 2
  • Hongwei Zhang
    • 1
  • Qingchuan Zhao
    • 1
  • Liu Hong
    • 1
  • Daiming Fan
    • 1
  1. 1.State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi’anChina
  2. 2.Air Force Military Medical UniversityXi’anChina

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