Molecular Biology

, Volume 52, Issue 2, pp 190–199 | Cite as

Overexpression of microRNAs miR-9, -98, and -199 Correlates with the Downregulation of HK2 Expression in Colorectal Cancer

  • A. V. Snezhkina
  • G. S. Krasnov
  • S. O. Zhikrivetskaya
  • I. Y. Karpova
  • M. S. Fedorova
  • K. M. Nyushko
  • M. M. Belyakov
  • N. V. Gnuchev
  • D. V. Sidorov
  • B. Y. Alekseev
  • N. V. Melnikova
  • A. V. Kudryavtseva
Genomics. Transcriptomics


Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from “The Cancer Genome Atlas” (TCGA) and five microRNA–mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software. Seven microRNAs containing binding site on mRNA HK2, which expression is negatively correlated with HK2 expression, were selected for further analysis. The expression levels of these microRNAs and mRNA HK2 were estimated by quantitative PCR on a set of CRC samples. It has been shown, that the expression of three microRNAs (miR-9-5p, -98-5p, and -199-5p) was increased and correlated negatively with mRNA level of HK2 gene. Thus, downregulation of HK2 gene may be caused by its negative regulation through microRNAs miR-9-5p, -98-5p, and -199-5p.


colorectal cancer microRNA HK2 glycolysis qPCR 



quantitative PCR


colorectal cancer


small noncoding RNA


miRNA sequencing


RNA sequencing


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  1. 1.
    El-Shami K., Oeffinger K.C., Erb N.L., et al. 2015. American Cancer Society colorectal cancer survivorship care guidelines. CA Cancer J. Clin. 65, 428–455.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kudryavtseva A.V., Lipatova A.V., Zaretsky A.R., et al. 2016. Important molecular genetic markers of colorectal cancer. Oncotarget. 7, 53959–53983.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Kim V.N. 2005. MicroRNA biogenesis: Coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 6, 376–385.CrossRefPubMedGoogle Scholar
  4. 4.
    Wang Y., Stricker H.M., Gou D. 2007. MicroRNA: Past and present. Front. Biosci. 12, 2316–2329.CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang C. 2008. MicroRNomics: A newly emerging approach for disease biology. Physiol. Genomics. 33, 139–147.CrossRefPubMedGoogle Scholar
  6. 6.
    Carthew R.W., Sontheimer E.J. 2009. Origins and mechanisms of miRNAs and siRNAs. Cell. 136, 642–655.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ha T.Y. 2011. MicroRNAs in human diseases: From cancer to cardiovascular disease. Immune Network. 11, 135–154.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    He Y., Lin J., Kong D., Huang M., et al. 2015. Current state of circulating microRNAs as cancer biomarkers. Clin. Chem. 61, 1138–1155.CrossRefPubMedGoogle Scholar
  9. 9.
    Clancy C., Joyce M.R., Kerin M.J. 2015. The use of circulating microRNAs as diagnostic biomarkers in colorectal cancer. Cancer Biomarkers. 15, 103–113.CrossRefPubMedGoogle Scholar
  10. 10.
    Skog J., Wurdinger T., van Rijn S., et al. 2008. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10, 1470–1476.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Valadi H., Ekstrom K., Bossios A., et al. 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell. Biol. 9, 654–659.CrossRefPubMedGoogle Scholar
  12. 12.
    Schetter A.J., Leung S.Y., Sohn J.J., et al. 2008. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. J. Am. Med. Assoc. 299, 425–436.Google Scholar
  13. 13.
    Bandres E., Agirre X., Bitarte N., et al. 2009. Epigenetic regulation of microRNA expression in colorectal cancer. Int. J. Cancer. 125, 2737–2743.CrossRefPubMedGoogle Scholar
  14. 14.
    Vogt M., Munding J., Gruner M., et al. 2011. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 458, 313–322.CrossRefPubMedGoogle Scholar
  15. 15.
    Selcuklu S.D., Donoghue M.T., Spillane C. 2009. miR-21 as a key regulator of oncogenic processes. Biochem. Soc. Trans. 37, 918–925.CrossRefPubMedGoogle Scholar
  16. 16.
    Toyota M., Suzuki H., Sasaki Y., et al. 2008. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 68, 4123–4132.CrossRefPubMedGoogle Scholar
  17. 17.
    de Krijger I., Mekenkamp L.J., Punt C.J., et al. 2011. MicroRNAs in colorectal cancer metastasis. J. Pathol. 224, 438–447.CrossRefPubMedGoogle Scholar
  18. 18.
    Kaller M., Liffers S.T., Oeljeklaus S., et al. 2011. Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis. Mol. Cell. Proteomics. 10, M111.010462.Google Scholar
  19. 19.
    Pullen T.J., da Silva Xavier G., Kelsey G., et al. 2011. miR-29a and miR-29b contribute to pancreatic beta cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol. Cell Biol. 31, 3182–3194.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hanahan D., Weinberg R.A. 2011. Hallmarks of cancer: The next generation. Cell. 144, 646–674.CrossRefPubMedGoogle Scholar
  21. 21.
    Warburg O. 1956. On the origin of cancer cells. Science. 123, 309–314.CrossRefPubMedGoogle Scholar
  22. 22.
    Moreno-Sanchez R., Rodriguez-Enriquez S., Saavedra E., et al. 2009. The bioenergetics of cancer: Is glycolysis the main ATP supplier in all tumor cells? Biofactors. 35, 209–225.CrossRefPubMedGoogle Scholar
  23. 23.
    Gatenby R.A., Gillies R.J. 2007. Glycolysis in cancer: A potential target for therapy. Int. J. Biochem. Cell Biol. 39, 1358–1366.CrossRefPubMedGoogle Scholar
  24. 24.
    Marin-Hernandez A., Gallardo-Perez J.C., Ralph S.J., et al. 2009. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini-Rev. Med. Chem. 9, 1084–1101.CrossRefPubMedGoogle Scholar
  25. 25.
    Schornack P.A., Gillies R.J. 2003. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors. Neoplasia. 5, 135–145.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Smallbone K., Gavaghan D.J., Gatenby R.A. et al. 2005. The role of acidity in solid tumour growth and invasion. J. Theor. Biol. 235, 476–484.CrossRefPubMedGoogle Scholar
  27. 27.
    Graziano F., Ruzzo A., Giacomini E., et al. 2017. Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer. Pharmacogenomics J. 17, 258–264.CrossRefPubMedGoogle Scholar
  28. 28.
    Oparina N.Y., Snezhkina A.V., Sadritdinova A.F., et al. 2013. Differential expression of genes that encode glycolysis enzymes in kidney and lung cancer in humans. Russ. J. Genet. 49, 707–716.CrossRefGoogle Scholar
  29. 29.
    Chan A.K., Bruce J.I., Siriwardena A.K. 2016. Glucose metabolic phenotype of pancreatic cancer. World J. Gastroenterol. 22, 3471–3485.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Krasnov G.S., Dmitriev A.A., Snezhkina A.V., Kudryavtseva A.V. 2013. Deregulation of glycolysis in cancer: glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target. Expert Opin. Ther. Targets. 17, 681–963.CrossRefPubMedGoogle Scholar
  31. 31.
    Snezhkina A.V., Krasnov G.S., Zaretsky A.R., et al. 2016. Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer. BMC Genomics. 17, 1011.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhao Y., Liu H., Riker A.I., et al. 2011. Emerging metabolic targets in cancer therapy. Front. Biosci. 16, 1844–1860.CrossRefGoogle Scholar
  33. 33.
    Patra K.C., Wang Q., Bhaskar P.T., et al. 2013. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell. 24, 213–228.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kudryavtseva A.V., Fedorova M.S., Zhavoronkov A., et al. 2016. Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells. BMC Genet. 17,156.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Krasnov G.S., Dmitriev A.A., Lakunina V.A., et al. 2013. Targeting VDAC-bound hexokinase II: A promising approach for concomitant anti-cancer therapy. Expert. Opin. Ther. Targets. 17, 1221–1233.CrossRefPubMedGoogle Scholar
  36. 36.
    Zhou P., Chen W.G., Li X.W. 2015. MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer. Am. J. Cancer Res. 5, 2056–2063.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Yoshino H., Enokida H., Itesako T., et al. 2013. Tumorsuppressive microRNA-143/145 cluster targets hexokinase-2 in renal cell carcinoma. Cancer Sci. 104, 1567–1574.CrossRefPubMedGoogle Scholar
  38. 38.
    Fang R., Xiao T., Fang Z., et al. 2012. MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. J. Biol. Chem. 287, 23227–23235.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Gregersen L.H., Jacobsen A., Frankel L.B., et al. 2012. MicroRNA-143 down-regulates hexokinase 2 in colon cancer cells. BMC Cancer. 12,232.CrossRefPubMedGoogle Scholar
  40. 40.
    Jiang S., Zhang L.F., Zhang H.W., et al. 2012. A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 31, 1985–1998.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Su J., Liang H., Yao W., et al. 2014. MiR-143 and miR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer. PLoS One. 9, e114420.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Qin Y., Cheng C., Lu H., et al. 2016. miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells. Biochem. Biophys. Res. Commun. 469, 37–43.CrossRefPubMedGoogle Scholar
  43. 43.
    Krasnov G.S., Dmitriev A.A., Melnikova N.V., et al. 2016. CrossHub: A tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms. Nucleic Acids Res. 44, e62.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Snezhkina A.V., Krasnov G.S., Lipatova A.V., et al. 2016. The dysregulation of polyamine metabolism in colorectal cancer is associated with overexpression of c-Myc and C/EBPbeta rather than enterotoxigenic Bacteroides fragilis infection. Oxid. Med. Cell Longevity. 2016, 2353560.CrossRefGoogle Scholar
  45. 45.
    Krasnov G.S., Oparina N.Y., Dmitriev A.A., Kudryavtseva A.V., Anedchenko E.A., Kondrat’eva T.T., Zabarovsky E.R., Senchenko V.N. 2011. RPN1, a new reference gene for quantitative data normalization in lung and kidney cancer. Mol Biol. 45 (2), 211–220.CrossRefGoogle Scholar
  46. 46.
    Krasnov G.S., Dmitriev A.A., Sadtritdinova A.F., et al. 2015. Evaluation of Gene Expression of Hexokinases in Colorectal Cancer with the Use of Bioinformatics Methods. Biofizika. 60 (6), 1050–6.PubMedGoogle Scholar
  47. 47.
    Fedorova M.S., Kudryavtseva A.V., Lakunina V.A., et al. 2015. Downregulation of OGDHL expression is associated with promoter hypermethylation in colorectal cancer. Mol. Biol. 49 (4), 608–617.CrossRefGoogle Scholar
  48. 48.
    Chang K.H., Mestdagh P., Vandesompele J., et al. 2010. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC Cancer. 10,173.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Melnikova N.V., Dmitriev A.A., Belenikin M.S., et al. 2016. Identification, expression analysis, and target prediction of flax genotroph microRNAs under normal and nutrient stress conditions. Front. Plant Sci. 7,399.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Dmitriev A.A., Kudryavtseva A.V., Krasnov G.S., et al. 2016. Gene expression profiling of flax (Linum usitatissimum L.) under edaphic stress. BMC Plant Biol. 16,237.CrossRefPubMedGoogle Scholar
  51. 51.
    Dmitriev A.A., Krasnov G.S., Rozhmina T.A., et al. 2016. Glutathione S-transferases and UDP-glycosyl transferases are involved in response to aluminum stress in flax. Front. Plant Sci. 7, 1920.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Tomczak K., Czerwinska P., Wiznerowicz M. 2015. The Cancer Genome Atlas (TCGA): An immeasurable source of knowledge. Contemp. Oncol. (Poznan). 19, A68–A77.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Han H.B., Gu J., Zuo H.J., et al. 2012. Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. J. Pathol. 226, 544–555.CrossRefPubMedGoogle Scholar
  54. 54.
    Cappuzzo F., Sacconi A., Landi L., et al. 2014. MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies. Clin. Colorectal Cancer. 13, 37–45.e4.CrossRefPubMedGoogle Scholar
  55. 55.
    Johnson S.M., Grosshans H., Shingara J., et al. 2005. RAS is regulated by the let-7 microRNA family. Cell. 120, 635–647.CrossRefPubMedGoogle Scholar
  56. 56.
    Shimizu S., Takehara T., Hikita H., et al. 2010. The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J. Hepatol. 52, 698–704.CrossRefPubMedGoogle Scholar
  57. 57.
    Motoyama K., Inoue H., Nakamura Y., et al. 2008. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin. Cancer Res. 14, 2334–2340.CrossRefPubMedGoogle Scholar
  58. 58.
    Roush S., Slack F.J. 2008. The let-7 family of microRNAs. Trends Cell Biol. 18, 505–516.CrossRefPubMedGoogle Scholar
  59. 59.
    Peschiaroli A., Giacobbe A., Formosa A., et al. 2013. miR-143 regulates hexokinase 2 expression in cancer cells. Oncogene. 32, 797–802.CrossRefPubMedGoogle Scholar
  60. 60.
    Yao M., Wang X., Tang Y., Zhang W., Cui B., Liu Q., Xing L. 2014. Dicer mediating the expression of miR-143 and miR-155 regulates hexokinase II associated cellular response to hypoxia. Am. J. Physiol.: Lung Cell. Mol. Physiol. 307, L829–L837.Google Scholar
  61. 61.
    Vinci S., Gelmini S., Mancini I., et al. 2013. Genetic and epigenetic factors in regulation of microRNA in colorectal cancers. Methods. 59, 138–146.CrossRefPubMedGoogle Scholar
  62. 62.
    Cekaite L., Rantala J.K., Bruun J., et al. 2012. MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer. Neoplasia. 14, 868–879.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Park Y.R., Lee S.T., Kim S.L., et al. 2016. MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer. Int. J. Oncol. 48, 2135–2143.CrossRefPubMedGoogle Scholar
  64. 64.
    Oberg A.L., French A.J., Sarver A.L., et al. 2011. miRNA expression in colon polyps provides evidence for a multihit model of colon cancer. PLoS One. 6, e20465.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Zhu M., Xu Y., Ge M., et al. 2015. Regulation of UHRF1 by microRNA-9 modulates colorectal cancer cell proliferation and apoptosis. Cancer Sci. 106, 833–839.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Gu S., Chan W.Y. 2012. Flexible and versatile as a chameleon-sophisticated functions of microRNA-199a. Int. J. Mol. Sci. 13, 8449–8466.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Jiang J., Gusev Y., Aderca I., et al. 2008. Association of microRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin. Cancer Res. 14, 419–427.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Jia X.Q., Cheng H.Q., Qian X., et al. 2012. Lentivirusmediated overexpression of microRNA-199a inhibits cell proliferation of human hepatocellular carcinoma. Cell. Biochem. Biophys. 62, 237–244.CrossRefPubMedGoogle Scholar
  69. 69.
    Hou J., Lin L., Zhou W., et al. 2011. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 19, 232–243.CrossRefPubMedGoogle Scholar
  70. 70.
    Iorio M.V., Visone R., Di Leva G., et al. 2007. MicroRNA signatures in human ovarian cancer. Cancer Res. 67, 8699–8707.CrossRefPubMedGoogle Scholar
  71. 71.
    Nam E.J., Yoon H., Kim S.W., et al. 2008. MicroRNA expression profiles in serous ovarian carcinoma. Clin. Cancer Res. 14, 2690–2695.CrossRefPubMedGoogle Scholar
  72. 72.
    Petrillo M., Zannoni G.F., Beltrame L., et al. 2016. Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy: a retrospective longitudinal analysis using matched tumor biopsies. Ann. Oncol. 27, 625–634.CrossRefPubMedGoogle Scholar
  73. 73.
    Tsukigi M., Bilim V., Yuuki K., et al. 2012. Re-expression of miR-199a suppresses renal cancer cell proliferation and survival by targeting GSK-3beta. Cancer Lett. 315, 189–197.CrossRefPubMedGoogle Scholar
  74. 74.
    Wang F., Zheng Z., Guo J., et al. 2010. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol. Oncol. 119, 586–593.CrossRefPubMedGoogle Scholar
  75. 75.
    Ichimi T., Enokida H., Okuno Y., et al. 2009. Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int. J. Cancer. 125, 345–352.CrossRefPubMedGoogle Scholar
  76. 76.
    Duan Z., Choy E., Harmon D., et al. 2011. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol. Cancer Ther. 10, 1337–1345.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Song G., Zeng H., Li J., et al. 2010. miR-199a regulates the tumor suppressor mitogen-activated protein kinase kinase kinase 11 in gastric cancer. Biol. Pharm. Bull. 33, 1822–1827.CrossRefPubMedGoogle Scholar
  78. 78.
    Lee J.W., Choi C.H., Choi J.J., et al. 2008. Altered microRNA expression in cervical carcinomas. Clin. Cancer Res. 14, 2535–2542.CrossRefPubMedGoogle Scholar
  79. 79.
    Garzon R., Volinia S., Liu C.G., et al. 2008. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 111, 3183–3189.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Siragam V., Rutnam Z.J., Yang W., et al. 2012. MicroRNA miR-98 inhibits tumor angiogenesis and invasion by targeting activin receptor-like kinase-4 and matrix metalloproteinase-11. Oncotarget. 3, 1370–1385.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Chen X., Xu Y., Liao X., et al. 2016. Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer. Tumour Biol. 37, 11927–11936.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Ni R., Huang Y., Wang J. 2015. miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of nonsmall-cell lung cancer. OncoTargets Ther. 8, 2689–2697.Google Scholar
  83. 83.
    Yang G., Zhang X., Shi J. 2015. MiR-98 inhibits cell proliferation and invasion of non-small cell carcinoma lung cancer by targeting PAK1. Int. J. Clin. Exp. Med. 8, 20135–20145.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Zhou D.H., Wang X., Feng Q. 2014. EGCG enhances the efficacy of cisplatin by downregulating hsa-miR-98-5p in NSCLC A549 cells. Nutr. Cancer. 66, 636–644.CrossRefPubMedGoogle Scholar
  85. 85.
    Li F., Li X.J., Qiao L., et al. 2014. miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6. Exp. Mol. Med. 46, e116.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Liu X., Zhang W., Guo H., et al. 2016. miR-98 functions as a tumor suppressor in salivary adenoid cystic carcinomas. OncoTargets Ther. 9, 1777–1786.CrossRefGoogle Scholar
  87. 87.
    Sampson V.B., Rong N.H., Han J., et al. 2007. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 67, 9762–9770.CrossRefPubMedGoogle Scholar
  88. 88.
    Secombe J., Pierce S.B., Eisenman R.N. 2004. Myc: A weapon of mass destruction. Cell. 117, 153–156.CrossRefPubMedGoogle Scholar
  89. 89.
    Du Y., Li Y., Lv H., et al. 2015. miR-98 suppresses tumor cell growth and metastasis by targeting IGF1R in oral squamous cell carcinoma. Int. J. Clin. Exp. Pathol. 8, 12252–12259.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Zhang S., Zhang C., Li Y., et al. 2011. miR-98 regulates cisplatin-induced A549 cell death by inhibiting TP53 pathway. Biomed. Pharmacother. 65, 436–442.CrossRefPubMedGoogle Scholar
  91. 91.
    Panda H., Chuang T.D., Luo X., et al. 2012. Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3. J. Clin. Endocrinol. Metab. 97, E1316–1326.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Wendler A., Keller D., Albrecht C., et al. 2011. Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells. Oncol. Rep. 25, 273–279.PubMedGoogle Scholar
  93. 93.
    Yao Y., Suo A.L., Li Z.F., et al. 2009. MicroRNA profiling of human gastric cancer. Mol. Med. Rep. 2, 963–970.PubMedGoogle Scholar
  94. 94.
    Deng Z.Q., Yin J.Y., Tang Q., et al. 2014. Over-expression of miR-98 in FFPE tissues might serve as a valuable source for biomarker discovery in breast cancer patients. Int. J. Clin. Exp. Pathol. 7, 1166–1171.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Kaelin W.G., Jr., Ratcliffe P.J. 2008. Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway. Mol. Cell. 30, 393–402.CrossRefPubMedGoogle Scholar
  96. 96.
    Semenza G.L. 1998. Hypoxia-inducible factor 1: Master regulator of O2 homeostasis. Curr. Opin. Genet. Dev. 8, 588–594.CrossRefPubMedGoogle Scholar
  97. 97.
    Cai Z., Zhou Y., Lei T., et al. 2009. Mammary serine protease inhibitor inhibits epithelial growth factorinduced epithelial-mesenchymal transition of esophageal carcinoma cells. Cancer. 115, 36–48.CrossRefPubMedGoogle Scholar
  98. 98.
    Owada S., Shimoda Y., Tsuchihara K., et al. 2013. Critical role of H2O2 generated by NOX4 during cellular response under glucose deprivation. PLoS One. 8, e56628.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Qin W., Li C., Zheng W., et al. 2015. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells. Oncotarget. 6, 39839–39854.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Hebert C., Norris K., Scheper M.A., et al. 2007. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol. Cancer. 6, 5.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • A. V. Snezhkina
    • 1
  • G. S. Krasnov
    • 1
  • S. O. Zhikrivetskaya
    • 1
  • I. Y. Karpova
    • 1
  • M. S. Fedorova
    • 1
  • K. M. Nyushko
    • 2
  • M. M. Belyakov
    • 2
  • N. V. Gnuchev
    • 3
  • D. V. Sidorov
    • 2
  • B. Y. Alekseev
    • 2
  • N. V. Melnikova
    • 1
  • A. V. Kudryavtseva
    • 1
    • 2
  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia
  2. 2.National Medical Research Radiological CenterMinistry of Health of the Russian FederationMoscowRussia
  3. 3.Institute of Gene BiologyRussian Academy of SciencesMoscowRussia

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