Abstract
MicroRNA (miRNAs), a class of small, endogenous non-coding RNA molecules of about 21-24 nucleotides in length, have unraveled a new modulatory network of RNAs that form an additional level of posttranscriptional gene regulation by targeting messenger RNAs (mRNAs). These miRNAs possess the ability to regulate gene expression by modulating the stability of mRNAs, controlling their translation rates, and consequently regulating protein synthesis. Substantial experimental evidence established the involvement of miRNAs in most biological processes like growth, differentiation, development, and metabolism in mammals including humans. An aberrant expression of miRNAs has been implicated in several pathologies, including cancer. The association of miRNAs with tumor growth, development, and metastasis depicts their potential as effective diagnostic and prognostic biomarkers. Furthermore, exploitation of the role of different miRNAs as oncogenes or tumor suppressors has aided in designing several miRNA-based therapeutic approaches for treating cancer patients whose clinical trials are underway. In this review, we aim to summarize the biogenesis of miRNAs and the dysregulations in these pathways that result in various pathologies and in some cases, resistance to drug treatment. We provide a detailed review of the miRNA expression signatures in different cancers along with their diagnostic and prognostic utility. Furthermore, we elaborate on the potential employment of miRNAs to enhance cancer cell apoptosis, regress tumor progression and even overcome miRNA-induced drug resistance.
Keywords: miRNAs, cancer, diagnosis, prognosis, therapy, biogenesis.
[2]
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843-54.
[3]
Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403(6772): 901-6.
[4]
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99(24): 15524-9.
[5]
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102(39): 13944-9.
[6]
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006; 6(4): 259-69.
[7]
Ben-Hamo R, Efroni S. MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype. Oncotarget 2015; 6(3): 1594-604.
[8]
Svoronos AA, Engelman DM, Slack FJ. OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res 2016; 76(13): 3666-70.
[9]
Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006; 13(12): 1097-101.
[10]
Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432(7014): 231-5.
[11]
Lee Y, Kim M, Han J, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004; 23(20): 4051-60.
[12]
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.
[13]
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281-97.
[14]
Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11(9): 597-610.
[15]
Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genomics 2010; 11(7): 537-61.
[17]
Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 2008; 30(4): 460-71.
[18]
Qin W, Shi Y, Zhao B, et al. miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One 2010; 5(2)e9429
[19]
Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007; 318(5858): 1931-4.
[22]
Khraiwesh B, Arif MA, Seumel GI, et al. Transcriptional control of gene expression by microRNAs. Cell 2010; 140(1): 111-22.
[23]
Fabbri M, Paone A, Calore F, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA 2012; 109(31): E2110-6.
[24]
He S, Chu J, Wu LC, et al. MicroRNAs activate natural killer cells through Toll-like receptor signaling. Blood 2013; 121(23): 4663-71.
[26]
Giraldez AJ, Cinalli RM, Glasner ME, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science 2005; 308(5723): 833-8.
[27]
Klein ME, Impey S, Goodman RH. Role reversal: the regulation of neuronal gene expression by microRNAs. Curr Opin Neurobiol 2005; 15(5): 507-13.
[28]
Naguibneva I, Ameyar-Zazoua M, Polesskaya A, et al. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 2006; 8(3): 278-84.
[29]
Ikeda S, Kong SW, Lu J, et al. Altered microRNA expression in human heart disease. Physiol Genomics 2007; 31(3): 367-73.
[30]
Carè A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13(5): 613-8.
[31]
Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 2007; 13(4): 486-91.
[32]
Zhang C. MicroRNAs: role in cardiovascular biology and disease. Clin Sci (Lond) 2008; 114(12): 699-706.
[33]
Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 2008; 105(5): 1516-21.
[34]
O’Connell RM, Rao DS, Chaudhuri AA, et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008; 205(3): 585-94.
[35]
Davidson-Moncada J, Papavasiliou FN, Tam W. MicroRNAs of the immune system: roles in inflammation and cancer. Ann N Y Acad Sci 2010; 1183: 183-94.
[36]
Tili E, Michaille JJ, Costinean S, Croce CM. MicroRNAs, the immune system and rheumatic disease. Nat Clin Pract Rheumatol 2008; 4(10): 534-41.
[37]
Dai Y, Huang YS, Tang M, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 2007; 16(12): 939-46.
[38]
Chang S, Wen S, Chen D, Jin P. Small regulatory RNAs in neurodevelopmental disorders. Hum Mol Genet 2009; 18(R1): R18-26.
[39]
Ardekani AM, Naeini MM. The Role of MicroRNAs in Human Diseases. Avicenna J Med Biotechnol 2010; 2(4): 161-79.
[42]
Truong AB, Kretz M, Ridky TW, Kimmel R, Khavari PA. p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 2006; 20(22): 3185-97.
[43]
Tiribuzi R, Crispoltoni L, Porcellati S, et al. miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer’s disease. Neurobiol Aging 2014; 35(2): 345-56.
[44]
Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, et al. miR-203 represses ‘stemness’ by repressing DeltaNp63. Cell Death Differ 2008; 15(7): 1187-95.
[45]
Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65(21): 9628-32.
[46]
Tagawa H, Seto M. A microRNA cluster as a target of genomic amplification in malignant lymphoma. Leukemia 2005; 19(11): 2013-6.
[47]
Mavrakis KJ, Wolfe AL, Oricchio E, et al. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 2010; 12(4): 372-9.
[48]
O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435(7043): 839-43.
[49]
Chang TC, Yu D, Lee YS, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 2008; 40(1): 43-50.
[50]
Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 2007; 26(5): 745-52.
[51]
Yamakuchi M, Lotterman CD, Bao C, et al. P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci USA 2010; 107(14): 6334-9.
[52]
Xiao J, Lin H, Luo X, Luo X, Wang Z. miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress. EMBO J 2011; 30(3): 524-32.
[53]
Zhang Y, Liao JM, Zeng SX, Lu H. p53 downregulates Down syndrome-associated DYRK1A through miR-1246. EMBO Rep 2011; 12(8): 811-7.
[54]
Fazi F, Rosa A, Fatica A, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 2005; 123(5): 819-31.
[55]
Fazi F, Racanicchi S, Zardo G, et al. Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell 2007; 12(5): 457-66.
[56]
Saito Y, Liang G, Egger G, 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.
[57]
Lujambio A, Calin GA, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 2008; 105(36): 13556-61.
[58]
Walz AL, Ooms A, Gadd S, et al. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer Cell 2015; 27(2): 286-97.
[59]
Iliou MS, da Silva-Diz V, Carmona FJ, et al. Impaired DICER1 function promotes stemness and metastasis in colon cancer. Oncogene 2014; 33(30): 4003-15.
[60]
Dome JS, Coppes MJ. Recent advances in Wilms tumor genetics. Curr Opin Pediatr 2002; 14(1): 5-11.
[61]
Melo SA, Moutinho C, Ropero S, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 2010; 18(4): 303-15.
[62]
Cummins JM, Velculescu VE. Implications of micro-RNA profiling for cancer diagnosis. Oncogene 2006; 25(46): 6220-7.
[63]
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther 2016; 1(1): 15004.
[64]
Conti A, Aguennouz M, La Torre D, et al. miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV astrocytic tumors. J Neurooncol 2009; 93(3): 325-32.
[65]
Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005; 65(16): 7065-70.
[66]
Negrini M, Rasio D, Hampton GM, Sabbioni S, Rattan S, Carter SL, et al. Definition and refinement of chromosome 11 regions of LOH in breast cancer: identification of a new region at 11q23-q24. Cancer Res 1995; 55(14): 3003-7.
[67]
White NM, Bao TT, Grigull J, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol 2011; 186(3): 1077-83.
[68]
Marton S, Garcia MR, Robello C, et al. Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia 2008; 22(2): 330-8.
[69]
Akao Y, Nakagawa Y, Kitade Y, Kinoshita T, Naoe T. Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci 2007; 98(12): 1914-20.
[70]
Nagel R, le Sage C, Diosdado B, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res 2008; 68(14): 5795-802.
[71]
Xi Y, Formentini A, Chien M, et al. Prognostic values of microRNAs in colorectal cancer. Biomark Insights 2006; 2: 113-21.
[72]
Michael MZ, O’ Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003; 1(12): 882-91.
[73]
Bandrés E, Cubedo E, Agirre X, et al. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 2006; 5: 29.
[74]
Garzon R, Garofalo M, Martelli MP, et al. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci USA 2008; 105(10): 3945-50.
[75]
Hu Z, Chen X, Zhao Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 2010; 28(10): 1721-6.
[76]
Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120(5): 635-47.
[77]
Venturini L, Battmer K, Castoldi M, et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood 2007; 109(10): 4399-405.
[78]
Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 2008; 93(5): 1600-8.
[79]
Visone R, Pallante P, Vecchione A, et al. Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene 2007; 26(54): 7590-5.
[80]
Gibcus JH, Tan LP, Harms G, et al. Hodgkin lymphoma cell lines are characterized by a specific miRNA expression profile. Neoplasia 2009; 11(2): 167-76.
[81]
Feber A, Xi L, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg 2008; 135(2): 255-60.
[82]
Petrocca F, Visone R, Onelli MR, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 2008; 13(3): 272-86.
[83]
Xia L, Zhang D, Du R, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 2008; 123(2): 372-9.
[84]
Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65(21): 9628-32.
[85]
Ichimi T, Enokida H, Okuno Y, et al. Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer 2009; 125(2): 345-52.
[86]
Ichimi T, Enokida H, Okuno Y, et al. Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer 2009; 125(2): 345-52.
[87]
Bryant RJ, Pawlowski T, Catto JW, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 2012; 106(4): 768-74.
[88]
Brase JC, Johannes M, Schlomm T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 2011; 128(3): 608-16.
[89]
Iorio MV, Visone R, Di Leva G, et al. MicroRNA signatures in human ovarian cancer. Cancer Res 2007; 67(18): 8699-707.
[90]
Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res 2008; 14(9): 2588-92.
[91]
Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 2010; 16(4): 360-4.
[92]
Caramuta S, Egyházi S, Rodolfo M, et al. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol 2010; 130(8): 2062-70.
[93]
Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 2010; 126(1): 73-80.
[94]
Wang J, Chen J, Chang P, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila) 2009; 2(9): 807-13.
[95]
Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev 2009; 18(1): 50-5.
[96]
Lulla RR, Costa FF, Bischof JM, Chou PM de. F.B.M.; Vanin, E.F.; Soares, M.B. Identification of differentially expressed microRNAs in osteosarcoma. Sarcoma 2011; 2011732690
[97]
Thayanithy V, Sarver AL, Kartha RV, et al. Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone 2012; 50(1): 171-81.
[98]
Fornari F, Milazzo M, Chieco P, et al. In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2. J Pathol 2012; 227(3): 275-85.
[99]
Ban J, Jug G, Mestdagh P, et al. Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing’s sarcoma. Oncogene 2011; 30(18): 2173-80.
[100]
Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120(5): 635-47.
[101]
Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci USA 2008; 105(10): 3903-8.
[102]
Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 2007; 21(9): 1025-30.
[103]
Kim SJ, Shin JY, Lee KD, et al. MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7. Breast Cancer Res 2012; 14(1): R14.
[104]
Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005; 65(14): 6029-33.
[105]
Olive V, Bennett MJ, Walker JC, et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev 2009; 23(24): 2839-49.
[106]
Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 2008; 68(19): 8164-72.
[107]
Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli S. MiR-125 in normal and malignant hematopoiesis. Leukemia 2012; 26(9): 2011-8.
[108]
Sun YM, Lin KY, Chen YQ. Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol 2013; 6: 6.
[109]
Tili E, Michaille JJ, Luo Z, et al. The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state. Blood 2012; 120(13): 2631-8.
[110]
Roberts AW, Seymour JF, Brown JR, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol 2012; 30(5): 488-96.
[111]
Trimarchi JM, Lees JA. Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 2002; 3(1): 11-20.
[112]
Coller HA, Forman JJ, Legesse-Miller A. “Myc’ed messages”: myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet 2007; 3(8)e146
[113]
He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature 2005; 435(7043): 828-33.
[114]
Du B, Wang Z, Zhang X, et al. MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells. PLoS One 2014; 9(2)e88022
[115]
Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature 2005; 435(7044): 974-8.
[116]
Gillies JK, Lorimer IA. Regulation of p27Kip1 by miRNA 221/222 in glioblastoma. Cell Cycle 2007; 6(16): 2005-9.
[117]
le Sage C, Nagel R, Egan DA, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 2007; 26(15): 3699-708.
[118]
Visone R, Russo L, Pallante P, et al. MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocr Relat Cancer 2007; 14(3): 791-8.
[119]
Lima RT, Busacca S, Almeida GM, Gaudino G, Fennell DA, Vasconcelos MH. MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer 2011; 47(2): 163-74.
[120]
Pichiorri F, Suh SS, Rocci A, et al. Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell 2010; 18(4): 367-81.
[121]
Yan HL, Xue G, Mei Q, et al. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J 2009; 28(18): 2719-32.
[122]
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102(39): 13944-9.
[123]
Denoyelle C, Lambert B, Meryet-Figuière M, et al. miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation. Cell Death Dis 2014; 5e1445
[124]
Zhang CZ, Zhang JX, Zhang AL, et al. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer 2010; 9: 229.
[125]
Hatley ME, Patrick DM, Garcia MR, et al. Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell 2010; 18(3): 282-93.
[126]
Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer 2009; 9(4): 293-302.
[127]
Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007; 449(7163): 682-8.
[128]
Kong W, Yang H, He L, et al. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol 2008; 28(22): 6773-84.
[129]
Bracken CP, Gregory PA, Kolesnikoff N, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 2008; 68(19): 7846-54.
[130]
Hurteau GJ, Carlson JA, Spivack SD, Brock GJ. Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res 2007; 67(17): 7972-6.
[131]
Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 2008; 283(22): 14910-4.
[132]
Tavazoie SF, Alarcón C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008; 451(7175): 147-52.
[133]
Xu Y, Zhao F, Wang Z, et al. MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1. Oncogene 2012; 31(11): 1398-407.
[134]
Lynch J, Fay J, Meehan M, et al. MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway. Carcinogenesis 2012; 33(5): 976-85.
[135]
Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002; 2(10): 795-803.
[136]
Liu F, Lou YL, Wu J, et al. Upregulation of microRNA-210 regulates renal angiogenesis mediated by activation of VEGF signaling pathway under ischemia/perfusion injury in vivo and in vitro. Kidney Blood Press Res 2012; 35(3): 182-91.
[137]
Liu LZ, Li C, Chen Q, et al. MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One 2011; 6(4)e19139
[138]
Lei Z, Li B, Yang Z, et al. Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One 2009; 4(10)e7629
[139]
Cha ST, Chen PS, Johansson G, et al. MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Cancer Res 2010; 70(7): 2675-85.
[140]
To KK, Robey RW, Knutsen T, Zhan Z, Ried T, Bates SE. Escape from hsa-miR-519c enables drug-resistant cells to maintain high expression of ABCG2. Mol Cancer Ther 2009; 8(10): 2959-68.
[141]
Kovalchuk O, Filkowski J, Meservy J, et al. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther 2008; 7(7): 2152-9.
[142]
Zhu H, Wu H, Liu X, et al. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol 2008; 76(5): 582-8.
[143]
Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene 2007; 26(19): 2799-803.
[144]
Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56(11): 1733-41.
[145]
Wu L, Zhou H, Lin H, et al. Circulating microRNAs are elevated in plasma from severe preeclamptic pregnancies. Reproduction 2012; 143(3): 389-97.
[146]
Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC, Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology 2011; 77(5): 1265.e9-1265.e16.
[147]
Baraniskin A, Kuhnhenn J, Schlegel U, et al. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro-oncol 2012; 14(1): 29-33.
[148]
Xie Y, Todd NW, Liu Z, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer 2010; 67(2): 170-6.
[149]
Yamada Y, Enokida H, Kojima S, et al. MiR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology. Cancer Sci 2011; 102(3): 522-9.
[150]
Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 2010; 50(4): 298-301.
[151]
Hu Z, Chen X, Zhao Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 2010; 28(10): 1721-6.
[152]
Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435(7043): 834-8.
[153]
du Rieu MC, Torrisani J, Selves J, et al. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem 2010; 56(4): 603-12.
[154]
Blenkiron C, Goldstein LD, Thorne NP, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007; 8(10): R214.
[155]
Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial–mesenchymal transition. Cell Cycle 2008; 7(5): 3112-8.
[156]
Li X, Zhang Y, Zhang Y, Ding J, Wu K, Fan D. Survival prediction of gastric cancer by a seven-microRNA signature. Gut 2010; 59(5): 579-85.
[157]
Caramuta S, Egyha’zi S, Rodolfo M, et al. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol 2010; 130: 2062-70.
[158]
Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009; 361(15): 1437-47.
[159]
Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008; 299(4): 425-36.
[160]
Giovannetti E, Funel N, Peters GJ, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res 2010; 70(11): 4528-38.
[161]
Zhou M, Liu Z, Zhao Y, et al. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem 2010; 285: 21496-2507.
[162]
Meng F, Henson R, Lang M, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006; 130(7): 2113-29.
[163]
Zhang B, Farwell MA. microRNAs: A new emerging class of players for disease diagnostics and gene therapy. J Cell Mol Med 2008; 12(1): 3-21.
[164]
Hutvágner G, Simard MJ, Mello CC, Zamore PD. Sequence-specific inhibition of small RNA function. PLoS Biol 2004; 2(4)E98
[165]
Krützfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005; 438(7068): 685-9.
[166]
Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004; 15(2): 185-97.
[167]
Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4(9): 721-6.
[168]
Nielsen PE, Egholm M, Berg RH, Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 1991; 254(5037): 1497-500.
[169]
Fabbri E, Brognara E, Borgatti M, et al. miRNA therapeutics: delivery and biological activity of peptide nucleic acids targeting miRNAs. Epigenomics 2011; 3(6): 733-45.
[170]
Li T, Li D, Sha J, Sun P, Huang Y. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun 2009; 383(3): 280-5.
[171]
Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene 2007; 26(19): 2799-803.
[172]
Hatley ME, Patrick DM, Garcia MR, et al. Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell 2010; 18(3): 282-93.
[173]
Park JK, Kogure T, Nuovo GJ, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res 2011; 71(24): 7608-16.
[174]
Ma L, Reinhardt F, Pan E, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 2010; 28(4): 341-7.
[175]
Henry JC, Azevedo-Pouly AC, Schmittgen TD. MicroRNA replacement therapy for cancer. Pharm Res 2011; 28(12): 3030-42.
[176]
Choung S, Kim YJ, Kim S, Park HO, Choi YC. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem Biophys Res Commun 2006; 342(3): 919-27.
[177]
Kitade Y, Akao Y. MicroRNAs and their therapeutic potential for human diseases: microRNAs, miR-143 and -145, function as anti-oncomirs and the application of chemically modified miR-143 as an anti-cancer drug. J Pharmacol Sci 2010; 114(3): 276-80.
[178]
Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA 2007; 104(39): 15472-7.
[179]
Liu C, Kelnar K, Liu B, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 2011; 17(2): 211-5.
[180]
Roccaro AM, Sacco A, Thompson B, et al. MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 2009; 113(26): 6669-80.
[181]
Lee SJ, Kim SJ, Seo HH, et al. Over-expression of miR-145 enhances the effectiveness of HSVtk gene therapy for malignant glioma. Cancer Lett 2012; 320(1): 72-80.
[182]
Trang P, Medina PP, Wiggins JF, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene 2010; 29(11): 1580-7.
[183]
Kota J, Chivukula RR, O’Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009; 137(6): 1005-17.
[184]
Yang YP, Chien Y, Chiou GY, et al. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials 2012; 33(5): 1462-76.
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