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Cellular and Molecular Life Sciences

, Volume 76, Issue 19, pp 3723–3744 | Cite as

Deregulated miRNAs in osteoporosis: effects in bone metastasis

  • Daniele BellaviaEmail author
  • F. Salamanna
  • L. Raimondi
  • A. De Luca
  • V. Carina
  • V. Costa
  • R. Alessandro
  • M. Fini
  • G. Giavaresi
Review

Abstract

Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.

Keywords

miRNA Osteoporosis Osteolysis Bone metastasis 

Abbreviations

3′UTR

3′ Untranslated region

AGO2

Argonaut 2

BC

Breast cancer

BMSCs

Bone-marrow mesenchymal stem cells

BMPs

Bone morphogenetic proteins

CNTF

Ciliary neurotrophic factor

DGCR8

Di George syndrome critical region gene 8

ESCC

Esophageal squamous cell carcinoma

GPC3

Glypican 3

IL

Interleukin

MM

Multiple myeloma

MMP

Matrix metalloproteinase

MTSS1

Metastasis suppressor protein 1

MiRNAs

MicroRNAs

NSCLC

Non-small-cell lung cancer

OB

Osteoblast

OC

Osteoclast

OPG

Osteoprotegerin

PC

Prostate cancer

PTH

Parathyroid hormone

PBMCs

Peripheral blood mononuclear cells

qRT-PCR

Quantitative real-time polymerase chain reaction

RANKL

Receptor activator of nuclear factor kappa-B ligand

SREs

Skeletal-related events

TGFβ

Transforming growth factor-beta

TNFα

Tumor necrosis factor alpha

Wnt

Wingless-type MMTV integration site family

Notes

Acknowledgements

Dr. Daniele Bellavia, Dr. Angela De Luca, Dr. Valeria Carina, Dr. Viviana Costa, and Dr. Lavinia Raimondi contributed to the manuscript by working at the Technology Platform of Tissue Engineering, Theranostics and Oncology (Lab.Manager Dr. Gianluca Giavaresi), a laboratory started-up by the Rizzoli Orthopedic Institute in Palermo (Italy) with the grants also of National Operative Program projects (PON, MIUR).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests. No benefits in any form were received or will be received from a commercial party related directly or indirectly to the subject of this article.

References

  1. 1.
    Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int 2015:421746Google Scholar
  2. 2.
    Komori T (2011) Signaling networks in RUNX2-dependent bone development. J Cell Biochem 112:750–755Google Scholar
  3. 3.
    Guntur AR, Rosen CJ (2013) IGF-1 regulation of key signaling pathways in bone. Bonekey Rep 2:437Google Scholar
  4. 4.
    Wu M, Chen G, Li YP (2016) TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res 4:16009Google Scholar
  5. 5.
    Larousserie F et al (2017) Frontline science: human bone cells as a source of IL-27 under inflammatory conditions: role of TLRs and cytokines. J Leukoc Biol 101:1289–1300Google Scholar
  6. 6.
    Yamada A et al (2007) Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts. Immunology 120:573–579Google Scholar
  7. 7.
    Silfverswärd CJ, Penno H, Frost A, Nilsson O, Ljunggren O (2010) Expression of markers of activity in cultured human osteoblasts: effects of interleukin-4 and interleukin-13. Scand J Clin Lab Investig 70:338–342Google Scholar
  8. 8.
    Forte GI et al (2009) Characterization of two alternative Interleukin(IL)-10 5′UTR mRNA sequences, induced by lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells. Mol Immunol 46:2161–2166Google Scholar
  9. 9.
    Zhang Q, Chen B, Yan F, Guo J, Zhu X, Ma S, Yang W (2014) Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases. Biomed Res Int 2014:284836Google Scholar
  10. 10.
    Bellavia D, Costa V, De Luca A, Maglio M, Pagani S, Fini M, Giavaresi G (2016) Vitamin D level between calcium-phosphorus homeostasis and immune system: new perspective in osteoporosis. Curr Osteoporos Rep.  https://doi.org/10.1007/s11914-016-0331-2 Google Scholar
  11. 11.
    Kraemer B, Rothmund R, Banys M, Krawczyk N, Solomayer EF, Mack C, Wallwiener D, Fehm T (2011) Impaired bone microenvironment: correlation between bone density and presence of disseminated tumor cells. Anticancer Res 31:4423–4428Google Scholar
  12. 12.
    Coleman R et al (2014) Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial. Lancet Oncol 15:997–1006Google Scholar
  13. 13.
    Ottewell PD, Wang N, Brown HK, Reeves KJ, Fowles CA, Croucher PI, Eaton CL, Holen I (2014) Zoledronic acid has differential antitumor activity in the pre- and postmenopausal bone microenvironment in vivo. Clin Cancer Res 20:2922–2932Google Scholar
  14. 14.
    Pagani S, Fini M, Giavaresi G, Salamanna F, Borsari V (2015) The active role of osteoporosis in the interaction between osteoblasts and bone metastases. Bone 79:176–182Google Scholar
  15. 15.
    Salamanna F et al (2016) An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells. Oncotarget 7:76966–76983Google Scholar
  16. 16.
    Salamanna F, Contartese D, Maglio M, Fini M (2016) A systematic review on in vitro 3D bone metastases models: a new horizon to recapitulate the native clinical scenario? Oncotarget 7:44803–44820Google Scholar
  17. 17.
    Salamanna F, Pagani S, Maglio M, Borsari V, Giavaresi G, Martelli AM, Buontempo F, Fini M (2016) Estrogen-deficient osteoporosis enhances the recruitment and activity of osteoclasts by breast cancer cells. Histol Histopathol 31:83–93Google Scholar
  18. 18.
    Salamanna F, Borsari V, Brogini S, Torricelli P, Cepollaro S, Cadossi M, Fini M (2017) A human 3D in vitro model to assess the relationship between osteoporosis and dissemination to bone of breast cancer tumor cells. J Cell Physiol 232:1826–1834Google Scholar
  19. 19.
    Salamanna F, Borsari V, Contartese D, Nicoli Aldini N, Fini M (2018) Link between estrogen deficiency osteoporosis and susceptibility to bone metastases: a way towards precision medicine in cancer patients. Breast 41:42–50Google Scholar
  20. 20.
    Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sGoogle Scholar
  21. 21.
    David Roodman G, Silbermann R (2015) Mechanisms of osteolytic and osteoblastic skeletal lesions. Bonekey Rep 4:753Google Scholar
  22. 22.
    Landgraf P et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414Google Scholar
  23. 23.
    Mizoguchi F et al (2010) Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem 109:866–875Google Scholar
  24. 24.
    Bartel DP (2018) Metazoan microRNAs. Cell 173:20–51Google Scholar
  25. 25.
    Bellavia D et al (2019) Deregulated miRNAs in bone health: epigenetic roles in osteoporosis. Bone 122:52–75.  https://doi.org/10.1016/j.bone.2019.02.013 Google Scholar
  26. 26.
    Li H et al (2009) A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Investig 119:3666–3677Google Scholar
  27. 27.
    Wang Y, Li L, Moore BT, Peng XH, Fang X, Lappe JM, Recker RR, Xiao P (2012) MiR-133a in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis. PLoS One 7:e34641Google Scholar
  28. 28.
    Wang X et al (2013) miR-214 targets ATF4 to inhibit bone formation. Nat Med 19:93–100Google Scholar
  29. 29.
    Yang N et al (2013) Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis. J Bone Miner Res 28:559–573Google Scholar
  30. 30.
    Chen S et al (2014) MicroRNA-125b suppresses the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Mol Med Rep 9:1820–1826Google Scholar
  31. 31.
    Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS, van Griensven M (2014) Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res 29:1718–1728Google Scholar
  32. 32.
    Li H, Wang Z, Fu Q, Zhang J (2014) Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients. Biomarkers 19:553–556Google Scholar
  33. 33.
    Chen C, Cheng P, Xie H, Zhou HD, Wu XP, Liao EY, Luo XH (2014) MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res 29:338–347Google Scholar
  34. 34.
    Cao Z, Moore BT, Wang Y, Peng XH, Lappe JM, Recker RR, Xiao P (2014) MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis. PLoS One 9:e97098Google Scholar
  35. 35.
    Krzeszinski JY et al (2014) miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature 512:431–435Google Scholar
  36. 36.
    Lv H, Sun Y, Zhang Y (2015) MiR-133 is involved in estrogen deficiency-induced osteoporosis through modulating osteogenic differentiation of mesenchymal stem cells. Med Sci Monit 21:1527–1534Google Scholar
  37. 37.
    Weilner S et al (2015) Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation. Bone 79:43–51Google Scholar
  38. 38.
    Garmilla-Ezquerra P, Sañudo C, Delgado-Calle J, Pérez-Nuñez MI, Sumillera M, Riancho JA (2015) Analysis of the bone microRNome in osteoporotic fractures. Calcif Tissue Int 96:30–37Google Scholar
  39. 39.
    De-Ugarte L et al (2015) MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones. BMC Med Genom 8:75Google Scholar
  40. 40.
    Kocijan R et al (2016) Circulating microRNA signatures in patients with idiopathic and postmenopausal osteoporosis and fragility fractures. J Clin Endocrinol Metab 101:4125–4134Google Scholar
  41. 41.
    Bedene A et al (2016) MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women. Wien Klin Wochenschr 128:519–526Google Scholar
  42. 42.
    You L, Pan L, Chen L, Gu W, Chen J (2016) MiR-27a is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis. Cell Physiol Biochem 39:253–265Google Scholar
  43. 43.
    Chen J et al (2016) Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis. Sci Rep 6:36347Google Scholar
  44. 44.
    Wang Q et al (2017) LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother 89:1178–1186Google Scholar
  45. 45.
    Yavropoulou MP, Anastasilakis AD, Makras P, Tsalikakis DG, Grammatiki M, Yovos JG (2017) Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures. Eur J Endocrinol 176:169–176Google Scholar
  46. 46.
    Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, van Griensven M (2017) miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep 7:15861Google Scholar
  47. 47.
    Jiménez-Ortega RF et al (2017) Identification of microRNAs in human circulating monocytes of postmenopausal osteoporotic Mexican-Mestizo women: a pilot study. Exp Ther Med 14:5464–5472Google Scholar
  48. 48.
    Chen YJ, Chang WA, Huang MS, Chen CH, Wang KY, Hsu YL, Kuo PL (2017) Identification of novel genes in aging osteoblasts using next-generation sequencing and bioinformatics. Oncotarget 8:113598–113613Google Scholar
  49. 49.
    Hu CH, Sui BD, Du FY, Shuai Y, Zheng CX, Zhao P, Yu XR, Jin Y (2017) miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice. Sci Rep 7:43191Google Scholar
  50. 50.
    Feichtinger X et al (2018) Bone-related circulating microRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their association to bone microstructure and histomorphometry. Sci Rep 8:4867Google Scholar
  51. 51.
    Liu H, Liu Q, Wu XP, He HB, Fu L (2018) MiR-96 regulates bone metabolism by targeting osterix. Clin Exp Pharmacol Physiol 45:602–613Google Scholar
  52. 52.
    Ren H et al (2018) miRNA-seq analysis of human vertebrae provides insight into the mechanism underlying GIOP. Bone 120:371–386Google Scholar
  53. 53.
    Wang C, He H, Wang L, Jiang Y, Xu Y (2018) Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK. Biochem Cell Biol 96:627–635Google Scholar
  54. 54.
    Ramírez-Salazar EG et al (2018) Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women. Gene 679:19–27Google Scholar
  55. 55.
    Aquino-Martinez R et al (2018) miR-219a-5p regulates Rorβ during osteoblast differentiation and in age-related bone loss. J Bone Miner Res 34:135–144.  https://doi.org/10.1002/jbmr.3586 Google Scholar
  56. 56.
    Mencía Castaño I, Curtin CM, Duffy GP, O'Brien FJ (2018) Harnessing a novel inhibitory role of miR-16 in osteogenesis by human mesenchymal stem cells for advanced scaffold-based bone tissue engineering. Tissue Eng Part A 25:24–33.  https://doi.org/10.1089/ten.TEA.2017.0460 Google Scholar
  57. 57.
    Mäkitie RE, Hackl M, Niinimäki R, Kakko S, Grillari J, Mäkitie O (2018) Altered microRNA profile in osteoporosis caused by impaired WNT signaling. J Clin Endocrinol Metab 103:1985–1996Google Scholar
  58. 58.
    Haider MT, Taipaleenmäki H (2018) Targeting the metastatic bone microenvironment by MicroRNAs. Front Endocrinol (Lausanne) 9:202Google Scholar
  59. 59.
    Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, Pantel K, Amadori D, Kang Y (2013) Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell 24:542–556Google Scholar
  60. 60.
    Stückrath I, Rack B, Janni W, Jäger B, Pantel K, Schwarzenbach H (2015) Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients. Oncotarget 6:13387–13401Google Scholar
  61. 61.
    Wang F, Zheng Z, Guo J, Ding X (2010) Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol 119:586–593Google Scholar
  62. 62.
    Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS (2011) Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 57:84–91Google Scholar
  63. 63.
    Mar-Aguilar F, Mendoza-Ramírez JA, Malagón-Santiago I, Espino-Silva PK, Santuario-Facio SK, Ruiz-Flores P, Rodríguez-Padilla C, Reséndez-Pérez D (2013) Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers 34:163–169Google Scholar
  64. 64.
    Matamala N et al (2015) Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin Chem 61:1098–1106Google Scholar
  65. 65.
    Liu X, Feng J, Tang L, Liao L, Xu Q, Zhu S (2015) The regulation and function of miR-21-FOXO3a-miR-34b/c signaling in breast cancer. Int J Mol Sci 16:3148–3162Google Scholar
  66. 66.
    Wang G, Wang L, Sun S, Wu J, Wang Q (2015) Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann Lab Med 35:226–232Google Scholar
  67. 67.
    Jurkovicova D et al (2016) Evaluation of expression profiles of microRNAs and two target genes, FOXO3a and RUNX2, effectively supports diagnostics and therapy predictions in breast cancer. Neoplasma 63:941–951Google Scholar
  68. 68.
    Liu B et al (2017) Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer. Hum Pathol 64:44–52Google Scholar
  69. 69.
    Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, Hu C (2013) Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol 139:223–229Google Scholar
  70. 70.
    Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, Luo H (2012) Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One 7:e34210Google Scholar
  71. 71.
    Chan M et al (2013) Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res 19:4477–4487Google Scholar
  72. 72.
    Liu J et al (2017) Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer. Sci Rep 7:40487Google Scholar
  73. 73.
    Schwarzenbach H, Milde-Langosch K, Steinbach B, Müller V, Pantel K (2012) Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res Treat 134:933–941Google Scholar
  74. 74.
    Maroni P, Puglisi R, Mattia G, Carè A, Matteucci E, Bendinelli P, Desiderio MA (2017) In bone metastasis miR-34a-5p absence inversely correlates with Met expression, while Met oncogene is unaffected by miR-34a-5p in non-metastatic and metastatic breast carcinomas. Carcinogenesis 38:492–503Google Scholar
  75. 75.
    Zeng Z, Chen X, Zhu D, Luo Z, Yang M (2017) Low expression of circulating microRNA-34c is associated with poor prognosis in triple-negative breast cancer. Yonsei Med J 58:697–702Google Scholar
  76. 76.
    Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688Google Scholar
  77. 77.
    Zhao FL, Hu GD, Wang XF, Zhang XH, Zhang YK, Yu ZS (2012) Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res 40:859–866Google Scholar
  78. 78.
    Bašová P, Pešta M, Sochor M, Stopka T (2017) Prediction potential of Serum miR-155 and miR-24 for relapsing early breast cancer. Int J Mol Sci 18:1–10.  https://doi.org/10.3390/ijms18102116 Google Scholar
  79. 79.
    Croset M et al (2018) miRNA-30 Family members inhibit breast cancer invasion, osteomimicry, and bone destruction by directly targeting multiple bone metastasis-associated genes. Cancer Res 78:5259–5273Google Scholar
  80. 80.
    Kong X, Zhang J, Li J, Shao J, Fang L (2018) MiR-130a-3p inhibits migration and invasion by regulating RAB5B in human breast cancer stem cell-like cells. Biochem Biophys Res Commun 501:486–493Google Scholar
  81. 81.
    Madhavan D et al (2016) Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis 37:461–470Google Scholar
  82. 82.
    van Schooneveld E et al (2012) Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers. Breast Cancer Res 14:R34Google Scholar
  83. 83.
    Ng EK et al (2013) Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One 8:e53141Google Scholar
  84. 84.
    Lin SC, Yu-Lee LY, Lin SH (2018) Osteoblastic factors in prostate cancer bone metastasis. Curr Osteoporos Rep 16:642–647Google Scholar
  85. 85.
    Guo X, Han T, Hu P, Zhu C, Wang Y, Chang S (2018) Five microRNAs in serum as potential biomarkers for prostate cancer risk assessment and therapeutic intervention. Int Urol Nephrol 50:2193–2200Google Scholar
  86. 86.
    Zhang HL et al (2011) Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate 71:326–331Google Scholar
  87. 87.
    Watahiki A, Macfarlane RJ, Gleave ME, Crea F, Wang Y, Helgason CD, Chi KN (2013) Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer. Int J Mol Sci 14:7757–7770Google Scholar
  88. 88.
    Bonci D et al (2016) A microRNA code for prostate cancer metastasis. Oncogene 35:1180–1192Google Scholar
  89. 89.
    Chen WY et al (2015) MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer. Oncotarget 6:441–457Google Scholar
  90. 90.
    Fang Y, Qiu J, Jiang ZB, Xu SR, Zhou ZH, He RL (2019) Increased serum levels of miR-214 in patients with PCa with bone metastasis may serve as a potential biomarker by targeting PTEN. Oncol Lett 17:398–405Google Scholar
  91. 91.
    Nishikawa R et al (2014) Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol 45:401–410Google Scholar
  92. 92.
    Zhu C, Hou X, Zhu J, Jiang C, Wei W (2018) Expression of miR-30c and miR-29b in prostate cancer and its diagnostic significance. Oncol Lett 16:3140–3144Google Scholar
  93. 93.
    Xu L, Zhong J, Guo B, Zhu Q, Liang H, Wen N, Yun W, Zhang L (2016) miR-96 promotes the growth of prostate carcinoma cells by suppressing MTSS1. Tumour Biol 37:12023–12032Google Scholar
  94. 94.
    Tsai YC, Chen WY, Siu MK, Tsai HY, Yin JJ, Huang J, Liu YN (2017) Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6. Cancer Lett 384:1–8Google Scholar
  95. 95.
    Siu MK, Tsai YC, Chang YS, Yin JJ, Suau F, Chen WY, Liu YN (2015) Transforming growth factor-β promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway. Oncogene 34:4767–4776Google Scholar
  96. 96.
    Singh PK et al (2014) Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients. Oncotarget 5:824–840Google Scholar
  97. 97.
    Wei J, Gao W, Zhu CJ, Liu YQ, Mei Z, Cheng T, Shu YQ (2011) Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin J Cancer 30:407–414Google Scholar
  98. 98.
    Shen J et al (2011) Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer 11:374Google Scholar
  99. 99.
    Zhao K, Cheng J, Chen B, Liu Q, Xu D, Zhang Y (2017) Circulating microRNA-34 family low expression correlates with poor prognosis in patients with non-small cell lung cancer. J Thorac Dis 9:3735–3746Google Scholar
  100. 100.
    Wang C et al (2015) A five-miRNA panel identified from a multicentric case-control study serves as a novel diagnostic tool for ethnically diverse non-small-cell lung cancer patients. EBioMedicine 2:1377–1385Google Scholar
  101. 101.
    Liu Y, Zhang G, Li H, Han L, Fu A, Zhang N, Zheng Y (2015) Serum microRNA-365 in combination with its target gene TTF-1 as a non-invasive prognostic marker for non-small cell lung cancer. Biomed Pharmacother 75:185–190Google Scholar
  102. 102.
    Silva J et al (2011) Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J 37:617–623Google Scholar
  103. 103.
    Zhu W, Liu X, He J, Chen D, Hunag Y, Zhang YK (2011) Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study. BMC Cancer 11:393Google Scholar
  104. 104.
    Fei X, Zhang J, Zhao Y, Sun M, Zhao H, Li S (2018) miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells. Oncol Lett 15:9081–9086Google Scholar
  105. 105.
    Wang T et al (2012) Cell-free microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer. PLoS One 7:e43268Google Scholar
  106. 106.
    Yuxia M, Zhennan T, Wei Z (2012) Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis. J Cancer Res Clin Oncol 138:2045–2050Google Scholar
  107. 107.
    Cui EH, Li HJ, Hua F, Wang B, Mao W, Feng XR, Li JY, Wang X (2013) Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin 34:309–313Google Scholar
  108. 108.
    Chen X et al (2012) Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int J Cancer 130:1620–1628Google Scholar
  109. 109.
    Zhang C et al (2010) Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem 56:1871–1879Google Scholar
  110. 110.
    Wu C et al (2014) Diagnostic and prognostic implications of a serum miRNA panel in oesophageal squamous cell carcinoma. PLoS One 9:e92292Google Scholar
  111. 111.
    Wu C, Li M, Hu C, Duan H (2014) Clinical significance of serum miR-223, miR-25 and miR-375 in patients with esophageal squamous cell carcinoma. Mol Biol Rep 41:1257–1266Google Scholar
  112. 112.
    Khazaei S, Nouraee N, Moradi A, Mowla SJ (2017) A novel signaling role for miR-451 in esophageal tumor microenvironment and its contribution to tumor progression. Clin Transl Oncol 19:633–640Google Scholar
  113. 113.
    Dong W, Li B, Wang J, Song Y, Zhang Z, Fu C, Zhang P (2016) Diagnostic and predictive significance of serum microRNA-7 in esophageal squamous cell carcinoma. Oncol Rep 35:1449–1456Google Scholar
  114. 114.
    Lin X, Xu XY, Chen QS, Huang C (2015) Clinical significance of microRNA-34a in esophageal squamous cell carcinoma. Genet Mol Res 14:17684–17691Google Scholar
  115. 115.
    Cui XB et al (2017) MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma. Oncotarget 8:92454–92469Google Scholar
  116. 116.
    Dong W, Li B, Wang Z, Zhang Z, Wang J (2015) Clinical significance of microRNA-24 expression in esophageal squamous cell carcinoma. Neoplasma 62:250–258Google Scholar
  117. 117.
    Lu YF et al (2018) Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC). J Exp Clin Cancer Res 37:301Google Scholar
  118. 118.
    Wang K, Chen D, Meng Y, Xu J, Zhang Q (2018) Clinical evaluation of 4 types of microRNA in serum as biomarkers of esophageal squamous cell carcinoma. Oncol Lett 16:1196–1204Google Scholar
  119. 119.
    Raimondi L et al (2015) Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. Oncotarget 6:13772–13789Google Scholar
  120. 120.
    Wang W et al (2015) Aberrant levels of miRNAs in bone marrow microenvironment and peripheral blood of myeloma patients and disease progression. J Mol Diagn 17:669–678Google Scholar
  121. 121.
    Hao M et al (2016) Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis. Oncotarget 7:19589–19600Google Scholar
  122. 122.
    Zhang YK et al (2011) Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1. Biochem Biophys Res Commun 414:233–239Google Scholar
  123. 123.
    Bellavia D et al (2018) Engineered exosomes: a new promise for the management of musculoskeletal diseases. Biochim Biophys Acta 1862:1893–1901Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.IRCCS Istituto Ortopedico RizzoliBolognaItaly
  2. 2.Laboratory of Preclinical and Surgical StudiesIRCCS Istituto Ortopedico RizzoliBolognaItaly
  3. 3.Section of Biology and Genetics, Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D)University of PalermoPalermoItaly
  4. 4.Institute of Biomedicine and Molecular Immunology (IBIM)National Research CouncilPalermoItaly

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