MicroRNAs, TGF-β signaling, and the inflammatory microenvironment in cancer

Tumor Biology

Volumn 37, Issue 1, 2016, Pages 115-125

  Guo, Lingling ^a   Zhang, Yongsheng ^b   Zhang, Lifeng ^c   Huang, Fengbo ^d   Li, Jinfan ^d   Wang, Shouli ^a,e  

^a MEDICAL COLLEGE OF SOOCHOW UNIVERSITY   (China)

^b THE SECOND AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

^c THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

^d THE SECOND AFFILIATED HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^e SOOCHOW UNIVERSITY   (China)

Author keywords

Cancer; Inflammatory microenvironment; MicroRNA; TGF signaling

Indexed keywords

MICRORNA; MICRORNA 10B; MICRORNA 125B; MICRORNA 126; MICRORNA 132; MICRORNA 146; MICRORNA 155; MICRORNA 181; MICRORNA 182; MICRORNA 183; MICRORNA 196; MICRORNA 203; MICRORNA 21; MICRORNA 210; MICRORNA 221; MICRORNA 27A; MICRORNA 34A; MICRORNA 450B; MICRORNA 451; MICRORNA 494; MICRORNA 584; SMAD PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CYTOKINE; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

BIOGENESIS; CANCER CELL; CANCER PROGNOSIS; CANCER RELATED INFLAMMATION; CANCER SURVIVAL; CELL FUNCTION; CYTOKINE PRODUCTION; EPIGENETICS; GENE EXPRESSION REGULATION; HUMAN; INFLAMMATION; INTRACELLULAR SIGNALING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TUMOR INFLAMMATORY MICROENVIRONMENT; TUMOR MICROENVIRONMENT; UPREGULATION; ANIMAL; GENETICS; IMMUNOLOGY; METABOLISM; MOUSE; NEOPLASM; SIGNAL TRANSDUCTION;

ANIMALS; CYTOKINES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INFLAMMATION; MICE; MICRORNAS; NEOPLASMS; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSFORMING GROWTH FACTOR BETA; TUMOR MICROENVIRONMENT; UP-REGULATION;

EID: 84946866487     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-015-4374-2     Document Type: Review

References (146)

1. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.
2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
3. Melo SA, Esteller M. Dysregulation of microRNAs in cancer: playing with fire. FEBS Lett. 2010;585:2087–99.
4. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.
5. Ventura A, Jacks T. MicroRNAs and cancer: short RNAs go a long way. Cell. 2009;136:586–91.
6. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.
7. Kloosterman WP, Plasterk RHA. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11:441–50.
8. Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martinez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J Off Publ Fed Am Soc Exp Biol. 2015;29:3595–611.
9. O'Connell RM, Rao DS, Baltimore D. MicroRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295–312.
10. Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell. 2012;148:1172–87.
11. Tili E, Michaille JJ, Calin GA. Expression and function of micro-RNAs in immune cells during normal or disease state. Int J Med Sci. 2008;5:73–9.
12. Sonkoly E, Stahle M, Pivarcsi A. MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol. 2008;33:312–5.
13. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.
14. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
15. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.
16. Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 2012;72:2162–71.
17. Zhou X, Tang J, Cao H, Fan H, Li B: Tissue resident regulatory t cells: novel therapeutic targets for human disease. Cell Mol Immunol 2015
18. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.
19. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013;33 Suppl 1:S79–84.
20. Tili E, Michaille JJ. Resveratrol, microRNAs, inflammation, and cancer. J Nucleic Acids. 2011;2011:102431.
21. Iorio MV, Croce CM. MicroRNA involvement in human cancer. Carcinogenesis. 2012;33:1126–33.
22. O'Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of toll-like receptor signalling. Nat Rev Immunol. 2011;11:163–75.
23. Butz H, Rácz K, Hunyady L, Patócs A. Crosstalk between tgf-β signaling and the microRNA machinery. Trends Pharmacol Sci. 2012;33:382–93.
24. Sivadas VP, Kannan S. The microRNA networks of tgfbeta signaling in cancer. Tumour Biol. 2014;35:2857–69.
25. Tili E, Croce CM, Michaille JJ. Mir-155: on the crosstalk between inflammation and cancer. Int Rev Immunol. 2009;28:264–84.
26. Jurkovicova D, Magyerkova M, Kulcsar L, Krivjanska M, Krivjansky V, Gibadulinova A, et al. Mir-155 as a diagnostic and prognostic marker in hematological and solid malignancies. Neoplasma. 2014;61:241–51.
27. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of mir-155 and mir-125b levels following lipopolysaccharide/tnf-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007;179:5082–9.
28. Xue H, Hua LM, Guo M, Luo JM. Ship1 is targeted by mir-155 in acute myeloid leukemia. Oncol Rep. 2014;32:2253–9.
29. Trotta R, Chen L, Ciarlariello D, Josyula S, Mao C, Costinean S, et al. Mir-155 regulates ifn-gamma production in natural killer cells. Blood. 2012;119:3478–85.
30. Yamada A, Horimatsu T, Okugawa Y, Nishida N, Honjo H, Ida H, et al. Serum mir-21, mir-29a and mir-125b are promising biomarkers for the early detection of colorectal neoplasia. Clin Cancer Res: Off J Am Assoc Cancer Res. 2015;21:4234–42.
31. Xu Z, Yu YQ, Ge YZ, Zhu JG, Zhu M, Zhao YC, et al. MicroRNA expression profiles in muscle-invasive bladder cancer: identification of a four-microRNA signature associated with patient survival. Tumour Biol. 2015;36:8159–66.
32. Luo S, Wang J, Ma Y, Yao Z, Pan H. Ppargamma inhibits ovarian cancer cells proliferation through upregulation of mir-125b. Biochem Biophys Res Commun. 2015;462:85–90.
33. Morelli E, Leone E, Cantafio ME, Di Martino MT, Amodio N, Biamonte L, et al. Selective targeting of irf4 by synthetic microrna-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo. Leukemia. 2015. doi:10.1038/leu.2015.124.
34. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, et al. Negative regulation of tlr4 via targeting of the proinflammatory tumor suppressor pdcd4 by the microRNA mir-21. Nat Immunol. 2010;11:141–7.
35. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving nf-kappab, lin28, let-7 microRNA, and il6 links inflammation to cell transformation. Cell. 2009;139:693–706.
36. Buscaglia LE, Li Y. Apoptosis and the target genes of microRNA-21. Chinese J Cancer. 2011;30:371–80.
37. Pfeffer SR, Yang CH, Pfeffer LM. The role of mir-21 in cancer. Drug Deve Res. 2015. doi:10.1002/ddr.21257.
38. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature. 2007;449:919–22.
39. Chen C, Zhang Y, Zhang L, Weakley SM, Yao Q. MicroRNA-196: critical roles and clinical applications in development and cancer. J Cell Mol Med. 2011;15:14–23.
40. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, Vouret-Craviari V, et al. A synonymous variant in irgm alters a binding site for mir-196 and causes deregulation of irgm-dependent xenophagy in crohn's disease. Nat Genet. 2011;43:242–5.
41. Yang G, Han D, Chen X, Zhang D, Wang L, Shi C, et al. Mir-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of ikappabalpha both in vitro and in vivo. Neuro-Oncology. 2014;16:652–61.
42. Qi J, Qiao Y, Wang P, Li S, Zhao W, Gao C. MicroRNA-210 negatively regulates lps-induced production of proinflammatory cytokines by targeting nf-kappab1 in murine macrophages. FEBS Lett. 2012;586:1201–7.
43. Dang K, Myers KA. The role of hypoxia-induced mir-210 in cancer progression. Int J Mol Sci. 2015;16:6353–72.
44. Wang J, Zhao J, Shi M, Ding Y, Sun H, Yuan F, et al. Elevated expression of mir-210 predicts poor survival of cancer patients: a systematic review and meta-analysis. PLoS One. 2014;9:e89223.
45. Chen WX, Ren LH, Shi RH. Implication of miRNAs for inflammatory bowel disease treatment: systematic review. World J Gastrointest Pathophysiol. 2014;5:63–70.
46. Ebrahimi F, Gopalan V, Smith RA, Lam AK. Mir-126 in human cancers: clinical roles and current perspectives. Exp Mol Pathol. 2014;96:98–107.
47. Chen H, Li L, Wang S, Lei Y, Ge Q, Lv N, et al. Reduced mir-126 expression facilitates angiogenesis of gastric cancer through its regulation on vegf-a. Oncotarget. 2014;5:11873–85.
48. Li D, Wang A, Liu X, Meisgen F, Grunler J, Botusan IR, et al. MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. J Clin Invest. 2015;125:3008–26.
49. Wang ZH, Zhang QS, Duan YL, Zhang JL, Li GF, Zheng DL. Tgf-beta induced mir-132 enhances the activation of tgf-beta signaling through inhibiting smad7 expression in glioma cells. Biochem Biophys Res Commun. 2015;463:187–92.
50. Labbaye C, Testa U. The emerging role of mir-146a in the control of hematopoiesis, immune function and cancer. J Hematol Oncol. 2012;5:13.
51. Li J, Yang H, Li Y, Liu Y, Chen S, Qi C, et al. MicroRNA-146 up-regulation predicts the prognosis of non-small cell lung cancer by miRNA in situ hybridization. Exp Mol Pathol. 2014;96:195–9.
52. Davis-Dusenbery BN, Hata A. Mechanisms of control of microRNA biogenesis. J Biochem. 2010;148:381–92.
53. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, et al. Pre-b cell proliferation and lymphoblastic leukemia/high-grade lymphoma in e(mu)-mir155 transgenic mice. Proc Natl Acad Sci U S A. 2006;103:7024–9.
54. Cremer TJ, Ravneberg DH, Clay CD, Piper-Hunter MG, Marsh CB, Elton TS, et al. Mir-155 induction by f. Novicida but not the virulent f. Tularensis results in ship down-regulation and enhanced pro-inflammatory cytokine response. PLoS One. 2009;4:e8508.
55. Bala S, Marcos M, Kodys K, Csak T, Catalano D, Mandrekar P, et al. Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (tnf{alpha}) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem. 2011;286:1436–44.
56. Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci U S A. 2003;100:8621–3.
57. Akhurst RJ, Derynck R. Tgf-beta signaling in cancer--a double-edged sword. Trends Cell Biol. 2001;11:S44–51.
58. Blahna MT, Hata A. Smad-mediated regulation of microRNA biosynthesis. FEBS Lett. 2012;586:1906–12.
59. Hata A, Davis BN. Control of microRNA biogenesis by tgfbeta signaling pathway-a novel role of smads in the nucleus. Cytokine Growth Factor Rev. 2009;20:517–21.
60. Davis BN, Hata A. Regulation of microRNA biogenesis: a miriad of mechanisms: cell communication and signaling. CCS. 2009;7:18.
61. Elston R, Inman GJ. Crosstalk between p53 and tgf-beta signalling. J Signal Transduct. 2012;2012:294097.
62. Davis BN, Hilyard AC, Lagna G, Hata A. Smad proteins control drosha-mediated microRNA maturation. Nature. 2008;454:56–61.
63. Heldin CH, Moustakas A. Role of smads in tgfbeta signaling. Cell Tissue Res. 2011;347:21–36.
64. Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A. Smad proteins bind a conserved RNA sequence to promote microRNA maturation by drosha. Mol Cell. 2010;39:373–84.
65. Wang W, Li J, Zhu W, Gao C, Jiang R, Li W, et al. MicroRNA-21 and the clinical outcomes of various carcinomas: a systematic review and meta-analysis. BMC Cancer. 2014;14:819.
66. Yu Y, Wang Y, Ren X, Tsuyada A, Li A, Liu LJ, et al. Context-dependent bidirectional regulation of the muts homolog 2 by transforming growth factor beta contributes to chemoresistance in breast cancer cells. Mol Cancer Res. 2010;8:1633–42.
67. Monfared H, Ziaee SA, Hashemitabar M, Khayatzadeh H, Kheyrollahi V, Tavallaei M, et al. Co-regulated expression of tgf-beta variants and mir-21 in bladder cancer. Urol J. 2013;10:981–7.
68. Hong L, Han Y, Zhang Y, Zhang H, Zhao Q, Wu K, et al. MicroRNA-21: a therapeutic target for reversing drug resistance in cancer. Expert Opin Ther Targets. 2013;17:1073–80.
69. Wang J, Li Y, Wang X, Jiang C. Ursolic acid inhibits proliferation and induces apoptosis in human glioblastoma cell lines u251 by suppressing tgf-beta1/mir-21/pdcd4 pathway. Basic Clin Pharmacol Toxicol. 2012;111:106–12.
70. Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST, et al. Tgfbeta-mediated upregulation of hepatic mir-181b promotes hepatocarcinogenesis by targeting timp3. Oncogene. 2010;29:1787–97.
71. Brockhausen J, Tay SS, Grzelak CA, Bertolino P, Bowen DG, d'Avigdor WM, et al. Mir-181a mediates tgf-beta-induced hepatocyte emt and is dysregulated in cirrhosis and hepatocellular cancer. Liver Int. 2014;35:240–53.
72. Wang Y, Yu Y, Tsuyada A, Ren X, Wu X, Stubblefield K, et al. Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and atm. Oncogene. 2011;30:1470–80.
73. Neel JC, Lebrun JJ. Activin and tgfbeta regulate expression of the microRNA-181 family to promote cell migration and invasion in breast cancer cells. Cell Signal. 2013;25:1556–66.
74. Liu Y, Lai L, Chen Q, Song Y, Xu S, Ma F, et al. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of pten. J Immunol. 2012;188:5500–10.
75. Li L, Li Z, Kong X, Xie D, Jia Z, Jiang W, et al. Down-regulation of microRNA-494 via loss of smad4 increases foxm1 and beta-catenin signaling in pancreatic ductal adenocarcinoma cells. Gastroenterology. 2014;147:485–97. e418.
76. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.
77. Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, et al. Therapeutic silencing of mir-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010;28:341–7.
78. Ma L. Role of mir-10b in breast cancer metastasis. Breast Cancer Res: BCR. 2010;12:210.
79. Han X, Yan S, Weijie Z, Feng W, Liuxing W, Mengquan L, et al. Critical role of mir-10b in transforming growth factor-beta1-induced epithelial-mesenchymal transition in breast cancer. Cancer Gene Ther. 2014;21:60–7.
80. Ouyang H, Gore J, Deitz S, Korc M. MicroRNA-10b enhances pancreatic cancer cell invasion by suppressing tip30 expression and promoting egf and tgf-beta actions. Oncogene. 2014;33:4664–74.
81. Min S, Li L, Zhang M, Zhang Y, Liang X, Xie Y, et al. Tgf-beta-associated mir-27a inhibits dendritic cell-mediated differentiation of th1 and th17 cells by tab3, p38 mapk, map2k4 and map2k7. Genes Immun. 2012;13:621–31.
82. Donatelli SS, Zhou JM, Gilvary DL, Eksioglu EA, Chen X, Cress WD, et al. Tgf-beta-inducible microRNA-183 silences tumor-associated natural killer cells. Proc Natl Acad Sci U S A. 2014;111:4203–8.
83. Song L, Liu L, Wu Z, Li Y, Ying Z, Lin C, et al. Tgf-beta induces mir-182 to sustain nf-kappab activation in glioma subsets. J Clin Invest. 2012;122:3563–78.
84. Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, 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;28:6773–84.
85. Gal H, Pandi G, Kanner AA, Ram Z, Lithwick-Yanai G, Amariglio N, et al. Mir-451 and imatinib mesylate inhibit tumor growth of glioblastoma stem cells. Biochem Biophys Res Commun. 2008;376:86–90.
86. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673–7.
87. Schoof CR, Botelho EL, Izzotti A, Vasques Ldos R. MicroRNAs in cancer treatment and prognosis. Am J Cancer Res. 2012;2:414–33.
88. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting zeb1 and sip1. Nat Cell Biol. 2008;10:593–601.
89. Truong HH, Xiong J, Ghotra VP, Nirmala E, Haazen L, Le Devedec SE, et al. Beta1 integrin inhibition elicits a prometastatic switch through the tgfbeta-mir-200-zeb network in e-cadherin-positive triple-negative breast cancer. Sci Signal. 2014;7:ra15.
90. Izumchenko EG, Chang X, Michailidi C, Kagohara LT, Ravi R, Paz K, et al. The tgfbeta-mir200-mig6 pathway orchestrates the emt-associated kinase switch that induces resistance to egfr inhibitors. Cancer Res. 2014;74:3995–4005.
91. Maroof H, Salajegheh A, Smith RA, Lam AK. MicroRNA-34 family, mechanisms of action in cancer: a review. Curr Cancer Drug Targets. 2014;14:737–51.
92. Dimopoulos K, Gimsing P, Gronbaek K. Aberrant microRNA expression in multiple myeloma. Eur J Haematol. 2013;91:95–105.
93. Yang P, Li Q-J, Feng Y, Zhang Y, Markowitz G, Ning S, et al. Tgf-β-mir-34a-ccl22 signaling-induced treg cell recruitment promotes venous metastases of hbv-positive hepatocellular carcinoma. Cancer Cell. 2012;22:291–303.
94. Sonkoly E, Wei T, Pavez Lorie E, Suzuki H, Kato M, Torma H, et al. Protein kinase c-dependent upregulation of mir-203 induces the differentiation of human keratinocytes. J Invest Dermatol. 2010;130:124–34.
95. Tian L, Li M, Ge J, Guo Y, Sun Y, Liu M, et al. Mir-203 is downregulated in laryngeal squamous cell carcinoma and can suppress proliferation and induce apoptosis of tumours. Tumour Biol. 2014;35:5953–63.
96. Xu M, Gu M, Zhang K, Zhou J, Wang Z, Da J. Mir-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of fgf2. Diagn Pathol. 2015;10:24.
97. Ding X, Park SI, McCauley LK, Wang CY. Signaling between transforming growth factor beta (tgf-beta) and transcription factor snai2 represses expression of microRNA mir-203 to promote epithelial-mesenchymal transition and tumor metastasis. J Biol Chem. 2013;288:10241–53.
98. Ueno K, Hirata H, Shahryari V, Chen Y, Zaman MS, Singh K, et al. Tumour suppressor microRNA-584 directly targets oncogene rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer. 2011;104:308–15.
99. Fils-Aime N, Dai M, Guo J, El-Mousawi M, Kahramangil B, Neel JC, et al. MicroRNA-584 and the protein phosphatase and actin regulator 1 (phactr1), a new signaling route through which transforming growth factor-beta mediates the migration and actin dynamics of breast cancer cells. J Biol Chem. 2013;288:11807–23.
100. Sun MM, Li JF, Guo LL, Xiao HT, Dong L, Wang F, et al. Tgf-[beta]1 suppression of microRNA-450b-5p expression: a novel mechanism for blocking myogenic differentiation of rhabdomyosarcoma. Oncogene. 2014;33:2075–86.
101. Martin J, Jenkins RH, Bennagi R, Krupa A, Phillips AO, Bowen T, et al. Post-transcriptional regulation of transforming growth factor beta-1 by microRNA-744. PLoS One. 2011;6:e25044.
102. Dogar AM, Towbin H, Hall J. Suppression of latent transforming growth factor (tgf)-beta1 restores growth inhibitory tgf-beta signaling through microRNAs. J Biol Chem. 2011;286:16447–58.
103. Dogar AM, Semplicio G, Guennewig B, Hall J. Multiple microRNAs derived from chemically synthesized precursors regulate thrombospondin 1 expression. Nucleic Acid Ther. 2014;24:149–59.
104. Braun J, Hoang-Vu C, Dralle H, Huttelmaier S. Downregulation of microRNAs directs the emt and invasive potential of anaplastic thyroid carcinomas. Oncogene. 2010;29:4237–44.
105. Masri S, Liu Z, Phung S, Wang E, Yuan YC, Chen S. The role of microRNA-128a in regulating tgfbeta signaling in letrozole-resistant breast cancer cells. Breast Cancer Res Treat. 2010;124:89–99.
106. Jiang X, Xiang G, Wang Y, Zhang L, Yang X, Cao L, et al. MicroRNA-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting tgf-beta rii. Mol Cells. 2012;33:545–51.
107. Feng B, Dong TT, Wang LL, Zhou HM, Zhao HC, Dong F, et al. Colorectal cancer migration and invasion initiated by microRNA-106a. PLoS One. 2012;7:e43452.
108. Lo SS, Hung PS, Chen JH, Tu HF, Fang WL, Chen CY, et al. Overexpression of mir-370 and downregulation of its novel target tgfbeta-rii contribute to the progression of gastric carcinoma. Oncogene. 2011;31:226–37.
109. Chu TH, Yang CC, Liu CJ, Lui MT, Lin SC, Chang KW. Mir-211 promotes the progression of head and neck carcinomas by targeting tgfbetarii. Cancer Lett. 2013;337:115–24.
110. Yu Y, Kanwar SS, Patel BB, Oh P-S, Nautiyal J, Sarkar FH, et al. MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (ttgf-β r2) in colon cancer cells. Carcinogenesis. 2012;33:68–76.
111. Mishra S, Deng JJ, Gowda PS, Rao MK, Lin CL, Chen CL, et al. Androgen receptor and microRNA-21 axis downregulates transforming growth factor beta receptor ii (tgfbr2) expression in prostate cancer. Oncogene. 2014;33:4097–106.
112. Keklikoglou I, Koerner C, Schmidt C, Zhang JD, Heckmann D, Shavinskaya A, et al. MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting nf-kappab and tgf-beta signaling pathways. Oncogene. 2011;31:4150–63.
113. Harazono Y, Muramatsu T, Endo H, Uzawa N, Kawano T, Harada K, et al. Mir-655 is an emt-suppressive microRNA targeting zeb1 and tgfbr2. PLoS One. 2013;8:e62757.
114. Jiang Z, Yin J, Fu W, Mo Y, Pan Y, Dai L, et al. MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting tgfbetar2 in nsclc. PLoS One. 2014;9:e94639.
115. Jiang F, Mu J, Wang X, Ye X, Si L, Ning S, et al. The repressive effect of mir-148a on tgf beta-smads signal pathway is involved in the glabridin-induced inhibition of the cancer stem cells-like properties in hepatocellular carcinoma cells. PLoS One. 2014;9:e96698.
116. Turcatel G, Rubin N, El-Hashash A, Warburton D. Mir-99a and mir-99b modulate tgf-β induced epithelial to mesenchymal plasticity in normal murine mammary gland cells. PLoS One. 2012;7:e31032.
117. Wu ZB, Cai L, Lin SJ, Lu JL, Yao Y, Zhou LF. The mir-92b functions as a potential oncogene by targeting on smad3 in glioblastomas. Brain Res. 2013;1529:16–25.
118. Geraldo MV, Yamashita AS, Kimura ET. MicroRNA mir-146b-5p regulates signal transduction of tgf-beta by repressing smad4 in thyroid cancer. Oncogene. 2012;31:1910–22.
119. Zhang Y, Fan K-J, Sun Q, Chen A-Z, Shen W-L, Zhao Z-H, et al. Functional screening for miRNAs targeting smad4 identified mir-199a as a negative regulator of tgf-β signalling pathway. Nucleic Acids Res. 2012;40:9286–97.
120. Hager M, Pedersen CC, Larsen MT, Andersen MK, Hother C, Gronbaek K, et al. MicroRNA-130a-mediated down-regulation of smad4 contributes to reduced sensitivity to tgf-beta1 stimulation in granulocytic precursors. Blood. 2011;118:6649–59.
121. Liu L, Nie J, Chen L, Dong G, Du X, Wu X, et al. The oncogenic role of microRNA-130a/301a/454 in human colorectal cancer via targeting smad4 expression. PLoS One. 2013;8:e55532.
122. Genovese G, Ergun A, Shukla SA, Campos B, Hanna J, Ghosh P, et al. MicroRNA regulatory network inference identifies mir-34a as a novel regulator of tgf-β signaling in glioblastoma. Cancer Disc. 2012;2:736–49.
123. Zhong H, Wang HR, Yang S, Zhong JH, Wang T, Wang C, et al. Targeting smad4 links microRNA-146a to the tgf-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line. Int J Hematol. 2010;92:129–35.
124. Rai D, Kim SW, McKeller MR, Dahia PL, Aguiar RC. Targeting of smad5 links microRNA-155 to the tgf-beta pathway and lymphomagenesis. Proc Natl Acad Sci U S A. 2010;107:3111–6.
125. Jiang D, Aguiar RC. MicroRNA-155 controls rb phosphorylation in normal and malignant b lymphocytes via the noncanonical tgf-beta1/smad5 signaling module. Blood. 2014;123:86–93.
126. Liu Y, Sun R, Lin X, Liang D, Deng Q, Lan K. Kaposi's sarcoma-associated herpesvirus-encoded microRNA mir-k12-11 attenuates transforming growth factor beta signaling through suppression of smad5. J Virol. 2012;86:1372–81.
127. Smith AL, Iwanaga R, Drasin DJ, Micalizzi DS, Vartuli RL, Tan AC, et al. The mir-106b-25 cluster targets smad7, activates tgf-beta signaling, and induces emt and tumor initiating cell characteristics downstream of six1 in human breast cancer. Oncogene. 2012;31:5162–71.
128. Xia H, Ooi LL, Hui KM. MicroRNA-216a/217-induced epithelial-mesenchymal transition targets pten and smad7 to promote drug resistance and recurrence of liver cancer. Hepatology. 2013;58:629–41.
129. Petrocca F, Vecchione A, Croce CM. Emerging role of mir-106b-25/mir-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191–4.
130. Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2f1-regulated microRNAs impair tgfbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.
131. Mestdagh P, Bostrom AK, Impens F, Fredlund E, Van Peer G, De Antonellis P, et al. The mir-17-92 microRNA cluster regulates multiple components of the tgf-beta pathway in neuroblastoma. Mol Cell. 2010;40:762–73.
132. Li J, Fu H, Xu C, Tie Y, Xing R, Zhu J, et al. Mir-183 inhibits tgf-beta1-induced apoptosis by downregulation of pdcd4 expression in human hepatocellular carcinoma cells. BMC Cancer. 2010;10:354.
133. Pollari S, Leivonen SK, Perala M, Fey V, Kakonen SM, Kallioniemi O. Identification of microRNAs inhibiting tgf-beta-induced il-11 production in bone metastatic breast cancer cells. PLoS One. 2012;7:e37361.
134. Jiang H, Jin C, Liu J, Hua D, Zhou F, Lou X, et al. Next generation sequencing analysis of miRNAs: miR-127-3p inhibits glioblastoma proliferation and activates tgf-beta signaling by targeting ski. OMICS. 2014;18:196–206.
135. Zhang YE. Non-smad pathways in tgf-beta signaling. Cell Res. 2009;19:128–39.
136. Mu Y, Gudey SK, Landstrom M. Non-smad signaling pathways. Cell Tissue Res. 2012;347:11–20.
137. Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA. The fusion of two worlds: non-coding RNAs and extracellular vesicles—diagnostic and therapeutic implications (review). Int J Oncol. 2015;46:17–27.
138. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–83.
139. Villarroya-Beltri C, Baixauli F, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3–13.
140. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, Lyle R, et al. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 2014;8:1432–46.
141. Le MT, Hamar P, Guo C, Basar E, Perdigao-Henriques R, Balaj L, et al. Mir-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest. 2014;124:5109–28.
142. Neviani P, Fabbri M. Exosomic microRNAs in the tumor microenvironment. Frontiers Med. 2015;2:47.
143. Eugenia CY: Interaction of salicylates and the other nonsteroidal anti-inflammatory agents with breast cancer endocrine treatment: Systematic review. Am J Clin Oncol 2014:in press.
144. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377:31–41.
145. Shi L, Wang L, Hou J, Zhu B, Min Z, Zhang M, et al. Targeting roles of inflammatory microenvironment in lung cancer and metastasis. Cancer Metastasis Rev. 2015;34:319–31.
146. Balkwill FR, Mantovani A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol. 2012;22:33–40.