MiRNA-based therapeutic intervention of cancer

Journal of Hematology & Oncology

Michela Garofalo¹  Peter Magee¹  Srivatsava Naidu¹ 

[1] Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

关键词: Cancer therapy;    Noncoding RNAs;   

Others  :  1217368
DOI  :  10.1186/s13045-015-0162-0

 received in 2015-03-10, accepted in 2015-05-28,  发布年份 2015

【 摘 要 】

MicroRNAs (miRNAs) are important modulators of eukaryotic gene expression. By targeting protein coding transcripts, miRNAs influence the cellular transcriptome and proteome, thus helping to determine cell fate. MiRNAs have emerged as crucial molecules in cancer research, in which recent studies have linked erratic expression of miRNAs to carcinogenesis and have provided solid evidence for their potential in cancer therapy. This review briefly summarises the recent knowledge on the involvement of miRNAs in tumourigenesis and reviews current studies on the therapeutic strategies and advances in the delivery of miRNAs.

【 授权许可】

   
2015 Naidu et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001; 294(5543):853-8.
• [2]Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33.
• [3]Djuranovic S, Nahvi A, Green R. A parsimonious model for gene regulation by miRNAs. Science. 2011; 331(6017):550-3.
• [4]Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014; 42(Database issue):D68-73.
• [5]Davis BN, Hata A. Regulation of microRNA biogenesis: a miRiad of mechanisms. Cell Commun Signal CCS. 2009; 7:18.
• [6]Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004; 18(24):3016-27.
• [7]Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004; 10(2):185-91.
• [8]Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001; 293(5531):834-8.
• [9]Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001; 15(20):2654-9.
• [10]Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K et al.. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005; 436(7051):740-4.
• [11]Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003; 115(2):199-208.
• [12]Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014; 15(8):509-24.
• [13]Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics. 2014; 2014:970607.
• [14]Fabian MR, Sonenberg N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol. 2012; 19(6):586-93.
• [15]Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009; 8:102.
• [16]Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011; 469(7330):336-42.
• [17]Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al.. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002; 99(24):15524-9.
• [18]Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014; 9:287-314.
• [19]Lagana A, Russo F, Sismeiro C, Giugno R, Pulvirenti A, Ferro A. Variability in the incidence of miRNAs and genes in fragile sites and the role of repeats and CpG islands in the distribution of genetic material. PLoS One. 2010; 5(6):e11166.
• [20]Weber B, Stresemann C, Brueckner B, Lyko F. Methylation of human microRNA genes in normal and neoplastic cells. Cell Cycle. 2007; 6(9):1001-5.
• [21]Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA et al.. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006; 9(6):435-43.
• [22]Jackstadt R, Hermeking H. MicroRNAs as regulators and mediators of c-MYC function. Biochim Biophys Acta. 2014.
• [23]Hunten S, Siemens H, Kaller M, Hermeking H. The p53/microRNA network in cancer: experimental and bioinformatics approaches. Adv Exp Med Biol. 2013; 774:77-101.
• [24]Jansson MD, Lund AH. MicroRNA and cancer. Molecular Oncol. 2012; 6(6):590-610.
• [25]Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME. The role of let-7 in cell differentiation and cancer. Endocr Relat Cancer. 2010; 17(1):F19-36.
• [26]Wang X, Cao L, Wang Y, Wang X, Liu N, You Y. Regulation of let-7 and its target oncogenes (Review). Oncol Lett. 2012; 3(5):955-60.
• [27]Misso G, Di Martino MT, De Rosa G, Farooqi AA, Lombardi A, Campani V et al.. Mir-34: a new weapon against cancer? Mol Therapy Nucleic Acids. 2014; 3: Article ID e194
• [28]Haneklaus M, Gerlic M, O'Neill LA, Masters SL. miR-223: infection, inflammation and cancer. J Intern Med. 2013; 274(3):215-26.
• [29]Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep. 2006; 16(4):845-50.
• [30]Takagi T, Iio A, Nakagawa Y, Naoe T, Tanigawa N, Akao Y. Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology. 2009; 77(1):12-21.
• [31]Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Rebeles J et al.. Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PLoS One. 2012; 7(12):e52397.
• [32]Wang Z, Cai H, Lin L, Tang M, Cai H. Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Pediatr Blood Cancer. 2014; 61(2):206-10.
• [33]Zhang ZC, Li YY, Wang HY, Fu S, Wang XP, Zeng MS et al.. Knockdown of miR-214 promotes apoptosis and inhibits cell proliferation in nasopharyngeal carcinoma. PLoS One. 2014; 9(1):e86149.
• [34]Wang S, Jiao B, Geng S, Ma S, Liang Z, Lu S. Combined aberrant expression of microRNA-214 and UBC9 is an independent unfavorable prognostic factor for patients with gliomas. Med Oncol. 2014; 31(1):767.
• [35]Chen DL, Wang ZQ, Zeng ZL, Wu WJ, Zhang DS, Luo HY et al.. Identification of microRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression. Hepatology. 2014; 60(2):598-609.
• [36]Sun YM, Lin KY, Chen YQ. Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol. 2013; 6:6.
• [37]Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006; 6(4):259-69.
• [38]Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J et al.. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008; 9(4):405-14.
• [39]Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 2010; 467(7311):86-90.
• [40]Zhang CM, Zhao J, Deng HY. MiR-155 promotes proliferation of human breast cancer MCF-7 cells through targeting tumor protein 53-induced nuclear protein 1. J Biomed Sci. 2013; 20:79.
• [41]Raza U, Zhang JD, Sahin O. MicroRNAs: master regulators of drug resistance, stemness, and metastasis. J Mol Med. 2014; 92(4):321-36.
• [42]Xue W, Dahlman JE, Tammela T, Khan OF, Sood S, Dave A et al.. Small RNA combination therapy for lung cancer. Proc Natl Acad Sci U S A. 2014; 111(34):E3553-61.
• [43]Kasinski AL, Kelnar K, Stahlhut C, Orellana E, Zhao J, Shimer E et al.. A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer. Oncogene. 2014.
• [44]Cortez MA, Valdecanas D, Zhang X, Zhan Y, Bhardwaj V, Calin GA et al.. Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol Therapy J Am Soc Gene Therapy. 2014; 22(8):1494-503.
• [45]Zhang S, Shan C, Kong G, Du Y, Ye L, Zhang X. MicroRNA-520e suppresses growth of hepatoma cells by targeting the NF-kappaB-inducing kinase (NIK). Oncogene. 2012; 31(31):3607-20.
• [46]He XX, Chang Y, Meng FY, Wang MY, Xie QH, Tang F et al.. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012; 31(28):3357-69.
• [47]Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010; 31(10):1726-33.
• [48]Sicard F, Gayral M, Lulka H, Buscail L, Cordelier P. Targeting miR-21 for the therapy of pancreatic cancer. Molecul Therapy J Am Soc Gene Therapy. 2013; 21(5):986-94.
• [49]Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H et al.. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. 2013; 335(1):168-74.
• [50]Yang MH, Yu J, Jiang DM, Li WL, Wang S, Ding YQ. MicroRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis. J Transl Med. 2014; 12:109.
• [51]Liu F, Gong J, Huang W, Wang Z, Wang M, Yang J et al.. MicroRNA-106b-5p boosts glioma tumorigensis by targeting multiple tumor suppressor genes. Oncogene. 2014; 33(40):4813-22.
• [52]Bronisz A, Wang Y, Nowicki MO, Peruzzi P, Ansari KI, Ogawa D et al.. Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Cancer Res. 2014; 74(3):738-50.
• [53]Xu S, Wei J, Wang F, Kong LY, Ling XY, Nduom E et al. Effect of miR-142-3p on the M2 macrophage and therapeutic efficacy against murine glioblastoma. J Natl Cancer Inst. 2014;106(8). doi:10.1093/jnci/dju162
• [54]Zhou W, Shi G, Zhang Q, Wu Q, Li B, Zhang Z. MicroRNA-20b promotes cell growth of breast cancer cells partly via targeting phosphatase and tensin homologue (PTEN). Cell Biosci. 2014; 4(1):62.
• [55]Mitamura T, Watari H, Wang L, Kanno H, Hassan MK, Miyazaki M et al.. Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET. Oncogenesis. 2013; 2: Article ID e40
• [56]Davis S, Lollo B, Freier S, Esau C. Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res. 2006; 34(8):2294-304.
• [57]Obad S, dos Santos CO, Petri A, Heidenblad M, Broom O, Ruse C et al.. Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet. 2011; 43(4):371-8.
• [58]Liu YP, Berkhout B. miRNA cassettes in viral vectors: problems and solutions. Biochim Biophys Acta. 2011; 1809(11–12):732-45.
• [59]Sun Y, Yin G. Cell-specific delivery of messenger RNA and microRNA by recombinant MS2 virus-like particles carrying cell-penetrating peptide. Appl Microbiol Biotechnol. 2014.
• [60]Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW et al.. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009; 137(6):1005-17.
• [61]Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL et al.. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010; 107(14):6328-33.
• [62]Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA. 2010; 16(11):2043-50.
• [63]Li P, Sheng C, Huang L, Zhang H, Huang L, Cheng Z et al.. MiR-183/-96/-182 cluster is up-regulated in most breast cancers and increases cell proliferation and migration. Breast Cancer Res BCR. 2014; 16(6):473.
• [64]Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C et al.. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature. 2015; 518(7537):107-10.
• [65]Tivnan A, Orr WS, Gubala V, Nooney R, Williams DE, McDonagh C et al.. Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One. 2012; 7(5):e38129.
• [66]Biodegradable polymer nanocarriers for therapeutic antisense microRNA delivery in living animals. 2012.
• [67]Chiou GY, Cherng JY, Hsu HS, Wang ML, Tsai CM, Lu KH et al.. Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial-mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. J Control Release Off Jo Control Release Soc. 2012; 159(2):240-50.
• [68]Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D et al.. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Therapy J Am Soc Gene Therapy. 2011; 19(6):1116-22.
• [69]Conde J, Edelman ER, Artzi N. Target-responsive DNA/RNA nanomaterials for microRNA sensing and inhibition: the jack-of-all-trades in cancer nanotheranostics? Adv Drug Deliv Rev. 2015; 81C:169-83.
• [70]Kim M, Kasinski AL, Slack FJ. MicroRNA therapeutics in preclinical cancer models. Lancet Oncol. 2011; 12(4):319-21.
• [71]Rothschild S. MicroRNA therapies in cancer. Mol Cell Therapies. 2014; 2(1):7.
• [72]Luo J, Meng C, Tang Y, Zhang S, Wan M, Bi Y et al.. miR-132/212 cluster inhibits the growth of lung cancer xenografts in nude mice. Int J Clin Exp Med. 2014; 7(11):4115-22.
• [73]Xie C, Han Y, Liu Y, Han L, Liu J. miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer. Int J Clin Exp Pathol. 2014; 7(11):7518-26.
• [74]Zhu X, Li H, Long L, Hui L, Chen H, Wang X et al.. miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin. 2012; 44(6):519-26.
• [75]Huang P, Ye B, Yang Y, Shi J, Zhao H. MicroRNA-181 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) by targeting Bcl-2. Tumour Biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014.
• [76]Ma ZL, Hou PP, Li YL, Wang DT, Yuan TW, Wei JL et al.. MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFbetaR2. Tumour Biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014.
• [77]Yin R, Zhang S, Wu Y, Fan X, Jiang F, Zhang Z et al.. MicroRNA-145 suppresses lung adenocarcinoma-initiating cell proliferation by targeting OCT4. Oncol Rep. 2011; 25(6):1747-54.
• [78]Yang Y, Meng H, Peng Q, Yang X, Gan R, Zhao L et al.. Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4. Cancer Gene Ther. 2014.
• [79]Zhang B, Liu T, Wu T, Wang Z, Rao Z, Gao J. MicroRNA-137 functions as a tumor suppressor in human non-small cell lung cancer by targeting SLC22A18. Int J Biol Macromol. 2014; 74C:111-8.
• [80]Li Z, Li D, Zhang G, Xiong J, Jie Z, Cheng H et al.. Methylation-associated silencing of microRNA-335 contributes tumor cell invasion and migration by interacting with RASA1 in gastric cancer. Am J Cancer Res. 2014; 4(6):648-62.
• [81]Xie J, Tan ZH, Tang X, Mo MS, Liu YP, Gan RL et al.. miR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis. World J Gastroenterol WJG. 2014; 20(46):17439-47.
• [82]Shen J, Xiao Z, Wu WK, Wang MH, To KF, Chen Y et al.. Epigenetic silencing of miR-490-3p reactivates the chromatin remodeler SMARCD1 to promote Helicobacter pylori-induced gastric carcinogenesis. Cancer Res. 2014.
• [83]Wang Z, Ma X, Cai Q, Wang X, Yu B, Cai Q et al.. MiR-199a-3p promotes gastric cancer progression by targeting ZHX1. FEBS Lett. 2014; 588(23):4504-12.
• [84]Zhang Z, Liu X, Feng B, Liu N, Wu Q, Han Y et al.. STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer. Oncogene. 2014.
• [85]Ke TW, Wei PL, Yeh KT, Chen WT, Cheng YW. MiR-92a promotes cell metastasis of colorectal cancer through PTEN-mediated PI3K/AKT pathway. Ann Surg Oncol. 2014.
• [86]Suto T, Yokobori T, Yajima R, Morita H, Fujii T, Yamaguchi S et al.. MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation. Carcinogenesis. 2014.
• [87]Cai L, Cai X. Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma. Diagn Pathol. 2014; 9(1):1000.
• [88]Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z et al.. miR-150-5p inhibits hepatoma cell migration and invasion by targeting MMP14. PLoS One. 2014; 9(12):e115577.
• [89]He X, Li J, Guo W, Liu W, Yu J, Song W et al. Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma. Oncotarget. 2014.
• [90]Wu Q, Liu HO, Liu YD, Liu WS, Pan D, Zhang WJ et al.. Decreased expression of hepatocyte nuclear factor 4alpha (Hnf4alpha)/microRNA-122 (miR-122) axis in hepatitis B virus-associated hepatocellular carcinoma enhances potential oncogenic GALNT10 protein activity. J Biol Chem. 2015; 290(2):1170-85.
• [91]Huang X, Hou J, Shen X, Huang C, Zhang X, Xie Y et al.. MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1. FEBS J. 2014.
• [92]Wang X, Li M, Wang Z, Han S, Tang X, Ge Y et al.. Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration and invasion of esophageal squamous cell carcinoma cells. J Biol Chem. 2014.
• [93]Liu R, Gu J, Jiang P, Zheng Y, Liu X, Jiang X et al.. DNMT1-microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9-EGFR-AKT signaling. Clinical Cancer Research: an official journal of the American Association for Cancer Research. 2014.
• [94]Jiang Y, Duan Y, Zhou H. MicroRNA-27a directly targets to inhibit cell proliferation in esophageal squamous cell carcinoma. Oncol Lett. 2015; 9(1):471-7.
• [95]Yim RL, Wong KY, Kwong YL, Loong F, Leung CY, Chu R et al.. Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin’s lymphomas. Oncotarget. 2014; 5(20):9770-82.
• [96]Song G, Song G, Ni H, Gu L, Liu H, Chen B et al.. Deregulated expression of miR-224 and its target gene: CD59 predicts outcome of diffuse large B-cell lymphoma patients treated with R-CHOP. Curr Cancer Drug Targets. 2014; 14(7):659-70.
• [97]Li Y, Choi PS, Casey SC, Dill DL, Felsher DW. MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state. Cancer Cell. 2014; 26(2):262-72.
• [98]Wang LS, Li L, Li L, Chu S, Shiang KD, Li M et al.. MicroRNA-486 regulates normal erythropoiesis and enhances growth and modulates drug response in CML progenitors. Blood. 2014.
• [99]Palacios F, Prieto D, Abreu C, Ruiz S, Morande P, Fernandez-Calero T et al. Dissecting CLL microenvironment signals in unmutated patients: microRNA-22 regulates PTEN/AKT/FOXO pathway in proliferative leukemic cells. Leukemia & lymphoma. 2014:1–15. doi:10.3109/10428194.2014.990900
• [100]Lin Y, Li D, Liang Q, Liu S, Zuo X, Li L et al.. miR-638 regulates differentiation and proliferation in leukemic cells by targeting cyclin-dependent kinase 2. J Biol Chem. 2014.
• [101]Yang Y, Song K, Chang H, Chen L. Decreased expression of microRNA-126 is associated with poor prognosis in patients with cervical cancer. Diagn Pathol. 2014; 9(1):1001.
• [102]Shishodia G, Verma G, Srivastava Y, Mehrotra R, Das BC, Bharti AC. Deregulation of microRNAs Let-7a and miR-21 mediate aberrant STAT3 signaling during human papillomavirus-induced cervical carcinogenesis: role of E6 oncoprotein. BMC Cancer. 2014; 14(1):996.
• [103]Shen Y, Zhou J, Li Y, Ye F, Wan X, Lu W et al.. miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT. PLoS One. 2014; 9(10):e109299.
• [104]Sohn EJ, Won G, Lee J, Lee S, Kim SH. Upregulation of miRNA3195 and miRNA374b mediates the anti-angiogenic properties of melatonin in hypoxic PC-3 prostate cancer cells. J Cancer Educ. 2015; 6(1):19-28.
• [105]Han G, Fan M, Zhang X. MicroRNA-218 inhibits prostate cancer cell growth and promotes apoptosis by repressing TPD52 expression. Biochem Biophys Res Commun. 2015; 456(3):804-9.
• [106]Mortensen MM, Hoyer S, Orntoft TF, Sorensen KD, Dyrskjot L, Borre M. High miR-449b expression in prostate cancer is associated with biochemical recurrence after radical prostatectomy. BMC Cancer. 2014; 14:859.
• [107]Cui J, Bi M, Overstreet A, Yang Y, Li H, Leng Y et al.. MiR-873 regulates ERalpha transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene. 2014.
• [108]Kleivi Sahlberg K, Bottai G, Naume B, Burwinkel B, Calin GA, Borresen-Dale A et al.. A serum microRNA signature predicts tumor relapse and survival in triple negative breast cancer patients. Clin Cancer Res: an official journal of the American Association for Cancer Research. 2014.
• [109]Huynh FC, Jones FE. MicroRNA-7 inhibits multiple oncogenic pathways to suppress HER2Delta16 mediated breast tumorigenesis and reverse trastuzumab resistance. PLoS One. 2014; 9(12):e114419.
• [110]Yuan J, Xiao G, Peng G, Liu D, Wang Z, Liao Y et al.. MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ. Biochem Biophys Res Commun. 2014.
• [111]Liu Q, Zou R, Zhou R, Gong C, Wang Z, Cai T et al.. miR-155 regulates glioma cells invasion and chemosensitivity by p38 isforms in vitro. J Cell Biochem. 2014.
• [112]Yao Y, Ma J, Xue Y, Wang P, Li Z, Li Z et al.. MiR-449a exerts tumor-suppressive functions in human glioblastoma by targeting Myc-associated zinc-finger protein. Mol Oncol. 2014.
• [113]Lopez-Bertoni H, Lal B, Li A, Caplan M, Guerrero-Cazares H, Eberhart CG et al.. DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2. Oncogene. 2014.