Skip to main content

Advertisement

SpringerLink
Log in

Restoring TGFβ1 pathway-related microRNAs: possible impact in metastatic prostate cancer development

  • Review
  • Published:
Tumor Biology

Abstract

In developed countries, prostate cancer (PC) is the neoplasia more frequently diagnosed in men. The signaling pathway induced by the transforming growth factor β1 (TGFβ1) has an important role in cell growth, differentiation, and development, the downregulation of this pathway being associated with cancer development. In PC, the activation of this signaling pathway is lost, resulting in favoring of tumor growth, proliferation, and evasion of apoptosis. Several studies have shown that microRNAs (miRNAs), small non-coding RNA, are closely associated with the development, invasion, and metastasis, suggesting that they have a critical role in cancer development. Recently, Smad proteins, the signal transducers of the TGFβ1 signaling pathway, were found to regulate miRNA expression, through both transcriptional and posttranscriptional mechanisms. In this review, we summarize the mechanisms underlying Smad-mediated regulation of miRNA biogenesis and the effects on cancer development, particularly in PC. We identify that TGFβ1-related miR-143, miR-145, miR-146a, and miR-199a may have a key role in the development of prostate cancer metastasis and the restoration of their expression may be a promising therapeutic strategy for PC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  3. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61:1079–92.

    Article  PubMed  Google Scholar 

  4. Semenas J, Allegrucci C, Boorjian SA, Mongan NP, Persson JL. Overcoming drug resistance and treating advanced prostate cancer. Curr Drug Targets. 2012;13:1308–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Kumar V, Cotran R, Collins T. Robbins and Cotran pathologic basis of disease, ed 7. 2005.

  6. Chen YC, Page JH, Chen R, Giovannucci E. Family history of prostate cancer and breast cancer and the risk of prostate cancer in the PSA era. Prostate. 2008;68:1582–91.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61–71.

    Article  PubMed  Google Scholar 

  8. Houlgatte A, Vincendeau S, Desfemmes F, Ramirez J, Benoist N, Bensalah K, et al. Use of [-2] pro PSA and phi index for early detection of prostate cancer: A prospective of 452 patients. Prog Urol J Assoc Fr Urol Soc Fr Urol. 2012;22:279–83.

    CAS  Google Scholar 

  9. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A. Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer. Clin Chem. 2013;59:306–14.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang J, Zhao H, Gao Y, Zhang W. Secretory miRNAs as novel cancer biomarkers. Biochim Biophys Acta. 1826;2012:32–43.

    Google Scholar 

  11. Hao Y, Zhao Y, Zhao X, He C, Pang X, Wu TC, et al. Improvement of prostate cancer detection by integrating the PSA test with miRNA expression profiling. Cancer Investig. 2011;29:318–24.

    Article  CAS  Google Scholar 

  12. Fontenete S, Silva J, Teixeira AL, Ribeiro R, Bastos E, Pina F, et al. Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis. Int Braz J Urol Off J Braz Soc Urol. 2011;37:719–26.

    Article  CAS  Google Scholar 

  13. Nam RK, Zhang W, Siminovitch K, Shlien A, Kattan MW, Klotz LH, et al. New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort. Cancer Biol Ther. 2011;12:997–1004.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Hirata H, Hinoda Y, Kikuno N, Kawamoto K, Dahiya AV, Suehiro Y, et al. Cxcl12 g801a polymorphism is a risk factor for sporadic prostate cancer susceptibility. Clin Cancer Res. 2007;13:5056–62.

    Article  CAS  PubMed  Google Scholar 

  15. Wang SK, Wang ZZ, Huang YF. [Advances in researches on the relationship between single nucleotide polymorphism and prostate cancer]. Zhonghua nan ke xue =. Natl J Androl. 2005;11:605–10.

    CAS  Google Scholar 

  16. Zhang HL, Yang LF, Zhu Y, Yao XD, Zhang SL, Dai B, et al. 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. 2011;71:326–31.

    Article  CAS  PubMed  Google Scholar 

  17. Hou X, Flaig TW. Redefining hormone sensitive disease in advanced prostate cancer. Adv Urol. 2012;2012:978531.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Nicolas Mottet JB. Michel Bolla, Steven Joniau, Malcolm Masone, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2011;59:572–83.

    Article  PubMed  Google Scholar 

  19. Silva FCd (ed) Recomendações clínicas no tratamento do carcinoma da próstata, Lisboa, 2013, pp 226.

  20. Saraon P, Jarvi K, Diamandis EP. Molecular alterations during progression of prostate cancer to androgen independence. Clin Chem. 2011;57:1366–75.

    Article  CAS  PubMed  Google Scholar 

  21. Attar RM, Takimoto CH, Gottardis MM. Castration-resistant prostate cancer: locking up the molecular escape routes. Clin Cancer Res. 2009;15:3251–5.

    Article  CAS  PubMed  Google Scholar 

  22. Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1:34–45.

    Article  CAS  PubMed  Google Scholar 

  23. Kavleen Sikand SB, Girish C. Shukla. MicroRNAs and androgen receptor 3′ untranslated region: a missing link in castration-resistant prostate cancer? Mol Cell Pharmacol. 2011;3:107–13.

    PubMed Central  PubMed  Google Scholar 

  24. Keith F. Decker DZ, Yuhong He, Tamara Bowman, John R. Edwards and Li Jia. Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions. Nucleic Acids Res. 2012:1–15.

  25. Lamont KR, Tindall DJ. Minireview: alternative activation pathways for the androgen receptor in prostate cancer. Mol Endocrinol. 2011;25:897–907.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Myles C, Hodgson IA, Anthony N. Hollenberg. Prostate cancer cells is independent of NCoR and SMRT activity of androgen receptor antagonist bicalutamide in corepressors. Cancer Res. 2007;67:8388–95.

    Article  Google Scholar 

  27. Amaral TM, Macedo D, Fernandes I, Costa L. Castration-resistant prostate cancer: mechanisms, targets, and treatment. Prostate Cancer. 2012;2012:327253.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Pienta KJ, Bradley D. Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res. 2006;12:1665–71.

    Article  CAS  PubMed  Google Scholar 

  29. Sen A, De Castro I, Defranco DB, Deng FM, Melamed J, Kapur P, et al. Paxillin mediates extranuclear and intranuclear signaling in prostate cancer proliferation. J Clin Invest. 2012;122:2469–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Zhu B, Kyprianou N. Transforming growth factor beta and prostate cancer. Cancer Treat Res. 2005;126:157–73.

    Article  PubMed  Google Scholar 

  31. Rojas A, Padidam M, Cress D, Grady WM. TGF-beta receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-beta. Biochim Biophys Acta. 2009;1793:1165–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Li Z, Habuchi T, Tsuchiya N, Mitsumori K, Wang L, Ohyama C, et al. Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10. Carcinogenesis. 2004;25:237–40.

    Article  CAS  PubMed  Google Scholar 

  33. Wikstrom P, Damber J, Bergh A. Role of transforming growth factor-beta1 in prostate cancer. Microsc Res Tech. 2001;52:411–9.

    Article  CAS  PubMed  Google Scholar 

  34. Blahna MT, Hata A. Smad-mediated regulation of microRNA biosynthesis. FEBS Lett. 2012;586:1906–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Connolly EC, Freimuth J, Akhurst RJ. Complexities of TGF-β targeted cancer therapy. Int J Biol Sci. 2012;8:964–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Heldin CH, Moustakas A. Role of Smads in TGFbeta signaling. Cell Tissue Res. 2012;347:21–36.

    Article  CAS  PubMed  Google Scholar 

  37. Bierie B, Moses HL. Transforming growth factor beta (TGF-beta) and inflammation in cancer. Cytokine Growth Factor Rev. 2010;21:49–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Itatani Y, Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, et al. Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1(+) myeloid cells and facilitate liver metastasis. Gastroenterology. 2013;145:1064–75. e1011.

    Article  CAS  PubMed  Google Scholar 

  39. Fleming NI, Jorissen RN, Mouradov D, Christie M, Sakthianandeswaren A, Palmieri M, et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013;73:725–35.

    Article  CAS  PubMed  Google Scholar 

  40. Bacman D, Merkel S, Croner R, Papadopoulos T, Brueckl W, Dimmler A. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study. BMC Cancer. 2007;7:156.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, et al. The type III TGF-β receptor suppresses breast cancer progression. J Clin Invest. 2007;117:206–17.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Yang G, Yang X. Smad4-mediated TGF-β signaling in tumorigenesis. Int J Biol Sci. 2010;6:1–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Teixeira AL, Gomes M, Nogueira A, Azevedo AS, Assis J, Dias F, et al. Improvement of a predictive model of castration-resistant prostate cancer: functional genetic variants in TGFbeta1 signaling pathway modulation. PLoS One. 2013;8:e72419.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Kim SJ, Im YH, Markowitz SD, Bang YJ. Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. Cytokine Growth Factor Rev. 2000;11:159–68.

    Article  CAS  PubMed  Google Scholar 

  45. Wikstrom P, Stattin P, Franck-Lissbrant I, Damber JE, Bergh A. Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate. 1998;37:19–29.

    Article  CAS  PubMed  Google Scholar 

  46. Butz H, Racz K, Hunyady L, Patocs A. Crosstalk between TGF-beta signaling and the microRNA machinery. Trends Pharmacol Sci. 2012;33:382–93.

    Article  CAS  PubMed  Google Scholar 

  47. Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008;454:56–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Long X, Miano JM. Transforming growth factor-beta1 (TGF-beta1) utilizes distinct pathways for the transcriptional activation of microRNA 143/145 in human coronary artery smooth muscle cells. J Biol Chem. 2011;286:30119–29.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Ma S, Chan YP, Kwan PS, Lee TK, Yan M, Tang KH, et al. MicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2. Cancer Res. 2011;71:583–92.

    Article  CAS  PubMed  Google Scholar 

  52. Shi XB, Tepper CG. deVere White RW. Cancerous miRNAs and their regulation. Cell Cycle. 2008;7:1529–38.

    Article  CAS  PubMed  Google Scholar 

  53. Sk A. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors. 2012;12:3359–69.

    Article  Google Scholar 

  54. Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012;3:311–30.

    Article  CAS  PubMed  Google Scholar 

  55. Slezak-Prochazka I, Durmus S, Kroesen BJ, van den Berg A. MicroRNAs, macrocontrol: regulation of miRNA processing. RNA. 2010;16:1087–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Teixeira AL, Ferreira M, Silva J, Gomes M, Dias F, Santos JI, Mauricio J, Lobo F, Medeiros R. Higher circulating expression levels of mir-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2013.

  57. Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol. 2009;4:199–227.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Davis BN, Hata A. Regulation of microRNA biogenesis: a miRiad of mechanisms. Cell Commun Signal CCS. 2009;7:18.

    Article  PubMed  Google Scholar 

  59. Elston R, Inman GJ. Crosstalk between p53 and TGF-beta signalling. J Signal Transduct. 2012;2012:294097.

    PubMed Central  PubMed  Google Scholar 

  60. McDonald RA, Hata A, MacLean MR, Morrell NW, Baker AH. MicroRNA and vascular remodelling in acute vascular injury and pulmonary vascular remodelling. Cardiovasc Res. 2012;93:594–604.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Bowen T, Jenkins RH, Fraser DJ. MicroRNAs, transforming growth factor beta-1, and tissue fibrosis. J Pathol. 2013;229:274–85.

    Article  CAS  PubMed  Google Scholar 

  62. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, et al. TGF-beta activates akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 2009;11:881–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Kato M, Wang L, Putta S, Wang M, Yuan H, Sun G, et al. Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. J Biol Chem. 2010;285:34004–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, et al. miR-200a prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes. 2011;60:280–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22:894–907.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5:115–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Davis-Dusenbery BN, Chan MC, Reno KE, Weisman AS, Layne MD, Lagna G, et al. Down-regulation of Kruppel-like factor-4 (klf4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4. J Biol Chem. 2011;286:28097–110.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Jurkin J, Schichl YM, Koeffel R, Bauer T, Richter S, Konradi S, et al. miR-146a is differentially expressed by myeloid dendritic cell subsets and desensitizes cells to TLR2-dependent activation. J Immunol. 2010;184:4955–65.

    Article  CAS  PubMed  Google Scholar 

  71. Bello-DeOcampo D, Tindall DJ. TGF-betal/Smad signaling in prostate cancer. Curr Drug Targets. 2003;4:197–207.

    Article  CAS  PubMed  Google Scholar 

  72. Paolo Fuzio PD. Monica Rutigliano, Michele Battaglia, et al. Regulation of TGF-b1 expression by androgen deprivation therapy of prostate cancer. Cancer Lett. 2012;318:135–44.

    Article  PubMed  Google Scholar 

  73. Zhang H, Cai X, Wang Y, Tang H, Tong D, Ji F. microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep. 2010;24:1363–9.

    CAS  PubMed  Google Scholar 

  74. Akao Y, Nakagawa Y, Iio A, Naoe T. Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells. Leuk Res. 2009;33:1530–8.

    Article  CAS  PubMed  Google Scholar 

  75. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460:705–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  76. Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y, et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009;28:1385–92.

    Article  CAS  PubMed  Google Scholar 

  77. Ni Y, Meng L, Wang L, Dong W, Shen H, Wang G, et al. MicroRNA-143 functions as a tumor suppressor in human esophageal squamous cell carcinoma. Gene. 2013;517:197–204.

    Article  CAS  PubMed  Google Scholar 

  78. Fuse M, Nohata N, Kojima S, Sakamoto S, Chiyomaru T, Kawakami K, et al. Restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1. Int J Oncol. 2011;38:1093–101.

    CAS  PubMed  Google Scholar 

  79. Szczyrba J, Loprich E, Wach S, Jung V, Unteregger G, Barth S, et al. The microRNA profile of prostate carcinoma obtained by deep sequencing. Molecular Cancer Res MCR. 2010;8:529–38.

    Article  CAS  PubMed  Google Scholar 

  80. Yin Y, Yan ZP, Lu NN, Xu Q, He J, Qian X, et al. Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1. Biochim Biophys Acta. 1829;2013:239–47.

    Google Scholar 

  81. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Lo U-G, Yang D, Hsieh J-T. The role of microRNAs in prostate cancer progression. Transl Androl Urol. 2013;2:228–41.

    Google Scholar 

  83. Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14:417–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Xu B, Wang N, Wang X, Tong N, Shao N, Tao J, et al. Mir-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate. 2012;72:1171–8.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang J, Zhang D, Wu GQ, Feng ZY, Zhu SM. Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression. Hepatobiliary Pancreat Dis Int. 2013;12:305–9.

  86. Daneshmand S, Quek ML, Lin E, Lee C, Cote RJ, Hawes D, et al. Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. Hum Pathol. 2007;38:1547–52.

    Article  CAS  PubMed  Google Scholar 

  87. He J, Jing Y, Li W, Qian X, Xu Q, Li FS, et al. Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis. PLoS One. 2013;8:e56647.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Landi L, Cappuzzo F. HER2 and lung cancer. Expert Rev Anticancer Ther. 2013;13:1219–28.

    Article  CAS  PubMed  Google Scholar 

  89. Carrion-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, et al. Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative her receptors and ligands. Int J Oncol. 2012;41:1128–38.

    CAS  PubMed  Google Scholar 

  90. Baek KH, Hong ME, Jung YY, Lee CH, Lee TJ, Park ES, et al. Correlation of AR, EGFR, and HER2 expression levels in prostate cancer: immunohistochemical analysis and chromogenic in situ hybridization. Cancer Res Treat Off J Korean Cancer Assoc. 2012;44:50–6.

    Google Scholar 

  91. Wu D, Huang HJ, He CN, Wang KY. MicroRNA-199a-3p regulates endometrial cancer cell proliferation by targeting mammalian target of rapamycin (mTOR). Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2013;23:1191–7.

    Article  Google Scholar 

  92. Fornari F, Milazzo M, Chieco P, Negrini M, Calin GA, Grazi GL, et al. Mir-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2010;70:5184–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the Liga Portuguesa Contra o Cancro-Centro Regional do Norte (Portuguese League Against Cancer) and FCT-Fundação para a Ciência e Tecnologia. ALT is a doctoral degree grant holder from FCT (SFRH/BD/47381/2008).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    Juliana Inês Santos, Ana Luísa Teixeira, Francisca Dias, Mónica Gomes, Augusto Nogueira, Joana Assis & Rui Medeiros

  2. Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal

    Juliana Inês Santos, Ana Luísa Teixeira, Francisca Dias, Mónica Gomes & Rui Medeiros

  3. Research Department, LPCC-Portuguese League Against Cancer (NRNorte), Estrada Interior da Circunvalação 6657, 4200-177, Porto, Portugal

    Mónica Gomes, Augusto Nogueira, Joana Assis & Rui Medeiros

  4. CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia 296, 4200-150, Porto, Portugal

    Rui Medeiros

Authors
  1. Juliana Inês Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Luísa Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisca Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mónica Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Augusto Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joana Assis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rui Medeiros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rui Medeiros.

Additional information

Juliana Inês Santos and Ana Luísa Teixeira contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santos, J.I., Teixeira, A.L., Dias, F. et al. Restoring TGFβ1 pathway-related microRNAs: possible impact in metastatic prostate cancer development. Tumor Biol. 35, 6245–6253 (2014). https://doi.org/10.1007/s13277-014-1887-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1887-z

Keywords

Search

Navigation