miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells

  • Authors:
    • Peng Zhou
    • Liang Ma
    • Jun Zhou
    • Min Jiang
    • Enyu Rao
    • Yong Zhao
    • Feng Guo
  • View Affiliations

  • Published online on: February 15, 2016     https://doi.org/10.3892/ijo.2016.3392
  • Pages: 1737-1748
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The mir-17-92 cluster consists of six mature miRNAs and is implicated in diverse human cancers by targeting mRNAs involved in distinct pathways that either promote or inhibit carcinogenesis. However, the molecular mechanism underlying the mir-17-92 cluster-mediated pro-tumorigenic or anti-tumorigenic effects has not been clearly elucidated in prostate cancer. In the present study, the role of the mir-17-92 cluster in diverse aspects of prostate cancer cells has been thoroughly investigated. Forced introduction of the mir-17-92 cluster into the androgen-independent DU145 prostate cancer cells evidently promoted cell growth due to disruption of the balance between cellular proliferation and apoptosis. Overexpression of the mir-17-92 cluster significantly improved the migration and invasion of the DU145 cells, attributed to the induction of integrin β-1. Notably, the mir-17-92 cluster conveyed chemo-resistance to cisplatin. We demonstrated that the mir-17-92 cluster suppressed the expression of inhibitor of the AKT signaling pathway and activated the AKT pathway subsequently, which played a central role in regulating cellular proliferation, apoptosis and chemo-resistance. Continuously activated ERK1/2 signaling also contributed importantly to these processes. The present study provides key evidence for crucial oncogenic role of the miR-17-92 cluster in prostate cancer cells. Further investigations are warranted to determine whether miR-17-92 cluster can be targeted for future treatment of human prostate cancer.

References

1 

Saini S, Majid S and Dahiya R: Diet, microRNAs and prostate cancer. Pharm Res. 27:1014–1026. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL and Visakorpi T: MicroRNA expression profiling in prostate cancer. Cancer Res. 67:6130–6135. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Sun T, Wang Q, Balk S, Brown M, Lee GS and Kantoff P: The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 69:3356–3363. 2009. View Article : Google Scholar : PubMed/NCBI

5 

He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, et al: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y and Seto M: Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 64:3087–3095. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Mogilyansky E and Rigoutsos I: The miR-17/92 cluster: A comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 20:1603–1614. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Mu P, Han YC, Betel D, Yao E, Squatrito M, Ogrodowski P, de Stanchina E, D'Andrea A, Sander C and Ventura A: Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 23:2806–2811. 2009. View Article : Google Scholar : PubMed/NCBI

10 

van Haaften G and Agami R: Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev. 24:1–4. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Conkrite K, Sundby M, Mukai S, Thomson JM, Mu D, Hammond SM and MacPherson D: miR-17-92 cooperates with RB pathway mutations to promote retinoblastoma. Genes Dev. 25:1734–1745. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, Ueda S, Takanashi M and Kuroda M: miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci. 102:2264–2271. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Osada H and Takahashi T: let-7 and miR-17-92: Small-sized major players in lung cancer development. Cancer Sci. 102:9–17. 2011. View Article : Google Scholar

14 

Cho WC: OncomiRs: The discovery and progress of microRNAs in cancers. Mol Cancer. 6:602007. View Article : Google Scholar : PubMed/NCBI

15 

Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, Eret V, Ludvikova M, Babjuk M, Novak K, Stolz J, et al: Importance of miR-20a expression in prostate cancer tissue. Anticancer Res. 30:3579–3583. 2010.PubMed/NCBI

16 

Sikand K, Slane SD and Shukla GC: Intrinsic expression of host genes and intronic miRNAs in prostate carcinoma cells. Cancer Cell Int. 9:212009. View Article : Google Scholar : PubMed/NCBI

17 

Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, Ferbeyre G and Chartrand P: An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 282:2135–2143. 2007. View Article : Google Scholar

18 

Watahiki A and Wang Y, Morris J, Dennis K, O'Dwyer HM, Gleave M, Gout PW and Wang Y: MicroRNAs associated with metastatic prostate cancer. PLoS One. 6:e249502011. View Article : Google Scholar : PubMed/NCBI

19 

Guo F, Kang S, Zhou P, Guo L, Ma L and Hou J: Maspin expression is regulated by the non-canonical NF-κB subunit in androgen-insensitive prostate cancer cell lines. Mol Immunol. 49:8–17. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Liu F, Zhou J, Zhou P, Chen W and Guo F: The ubiquitin ligase CHIP inactivates NF-κB signaling and impairs the ability of migration and invasion in gastric cancer cells. Int J Oncol. 46:2096–2106. 2015.PubMed/NCBI

21 

Olive V, Li Q and He L: mir-17-92: A polycistronic oncomir with pleiotropic functions. Immunol Rev. 253:158–166. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL and Rajewsky K: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 9:405–414. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Wong P, Iwasaki M, Somervaille TC, Ficara F, Carico C, Arnold C, Chen CZ and Cleary ML: The miR-17-92 microRNA polycistron regulates MLL leukemia stem cell potential by modulating p21 expression. Cancer Res. 70:3833–3842. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Nittner D, Lambertz I, Clermont F, Mestdagh P, Köhler C, Nielsen SJ, Jochemsen A, Speleman F, Vandesompele J, Dyer MA, et al: Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation. Nat Cell Biol. 14:958–965. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y and Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65:9628–9632. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Zhu H, Han C and Wu T: MiR-17-92 cluster promotes hepatocarcinogenesis. Carcinogenesis. 36:1213–1222. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Zhu H, Han C, Lu D and Wu T: miR-17-92 cluster promotes cholangiocarcinoma growth: Evidence for PTEN as downstream target and IL-6/Stat3 as upstream activator. Am J Pathol. 184:2828–2839. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Wu Q, Luo G, Yang Z, Zhu F, An Y, Shi Y and Fan D: miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells. FEBS Lett. 588:2055–2062. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Park D, Lee SC, Park JW, Cho SY and Kim HK: Overexpression of miR-17 in gastric cancer is correlated with proliferation-associated oncogene amplification. Pathol Int. 64:309–314. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Grillari J, Hackl M and Grillari-Voglauer R: miR-17-92 cluster: Ups and downs in cancer and aging. Biogerontology. 11:501–506. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Krysan K, Kusko R, Grogan T, O'Hearn J, Reckamp KL, Walser TC, Garon EB, Lenburg ME, Sharma S, Spira AE, et al: PGE2-driven expression of c-Myc and oncomiR-17-92 contributes to apoptosis resistance in NSCLC. Mol Cancer Res. 12:765–774. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, et al: Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 26:6099–6105. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI, Nakazawa Y, Hayashi T, Ohtsuru A and Yamashita S: Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 99:1147–1154. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, Reifenberger G, Herold-Mende C, Lichter P and Radlwimmer B: De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene. 29:3411–3422. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, Li QJ, Lowe SW, Hannon GJ and He L: miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 23:2839–2849. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, He L, Ellison D, Gilbertson RJ, Hannon G, et al: The miR-17-92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci USA. 106:2812–2817. 2009. View Article : Google Scholar

37 

Gupta S, Read DE, Deepti A, Cawley K, Gupta A, Oommen D, Verfaillie T, Matus S, Smith MA, Mott JL, et al: Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis. 3:e3332012. View Article : Google Scholar : PubMed/NCBI

38 

Gantier MP, Stunden HJ, McCoy CE, Behlke MA, Wang D, Kaparakis-Liaskos M, Sarvestani ST, Yang YH, Xu D, Corr SC, et al: A miR-19 regulon that controls NF-κB signaling. Nucleic Acids Res. 40:8048–8058. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Trenkmann M, Brock M, Gay RE, Michel BA, Gay S and Huber LC: Tumor necrosis factor α-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-κB signaling. Arthritis Rheum. 65:916–927. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Li Y, Choi PS, Casey SC, Dill DL and Felsher DW: MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state. Cancer Cell. 26:262–272. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Li H, Bian C, Liao L, Li J and Zhao RC: miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1. Breast Cancer Res Treat. 126:565–575. 2011. View Article : Google Scholar

42 

Cohen R, Greenberg E, Nemlich Y, Schachter J and Markel G: miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1. Oncotarget. 6:19006–19016. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Wu Q, Yang Z, An Y, Hu H, Yin J, Zhang P, Nie Y, Wu K, Shi Y and Fan D: MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1. Cell Death Dis. 5:e11442014. View Article : Google Scholar : PubMed/NCBI

44 

Ohyagi-Hara C, Sawada K, Kamiura S, Tomita Y, Isobe A, Hashimoto K, Kinose Y, Mabuchi S, Hisamatsu T, Takahashi T, et al: miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression. Am J Pathol. 182:1876–1889. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Barkan D and Chambers AF: β1-integrin: A potential therapeutic target in the battle against cancer recurrence. Clin Cancer Res. 17:7219–7223. 2011. View Article : Google Scholar : PubMed/NCBI

46 

Kato H, Liao Z, Mitsios JV, Wang HY, Deryugina EI, Varner JA, Quigley JP and Shattil SJ: The primacy ofβ1 integrin activation in the metastatic cascade. PLoS One. 7:e465762012. View Article : Google Scholar

47 

Lee YC, Jin JK, Cheng CJ, Huang CF, Song JH, Huang M, Brown WS, Zhang S, Yu-Lee LY, Yeh ET, et al: Targeting constitutively activated β1 integrins inhibits prostate cancer metastasis. Mol Cancer Res. 11:405–417. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Somanath PR, Kandel ES, Hay N and Byzova TV: Akt1 signaling regulates integrin activation, matrix recognition, and fibronectin assembly. J Biol Chem. 282:22964–22976. 2007. View Article : Google Scholar : PubMed/NCBI

49 

Dhar S, Gu FX, Langer R, Farokhzad OC and Lippard SJ: Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci USA. 105:17356–17361. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Dhar S, Kolishetti N, Lippard SJ and Farokhzad OC: Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci USA. 108:1850–1855. 2011. View Article : Google Scholar : PubMed/NCBI

51 

Jacobsen C and Honecker F: Cisplatin resistance in germ cell tumours: Models and mechanisms. Andrology. 3:111–121. 2015. View Article : Google Scholar

52 

Jiang Z, Yin J, Fu W, Mo Y, Pan Y, Dai L, Huang H, Li S and Zhao J: MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting TGFbetaR2 in NSCLC. PLoS One. 9:e946392014. View Article : Google Scholar : PubMed/NCBI

53 

Wang X, Martindale JL and Holbrook NJ: Requirement for ERK activation in cisplatin-induced apoptosis. J Biol Chem. 275:39435–39443. 2000. View Article : Google Scholar : PubMed/NCBI

54 

Persons DL, Yazlovitskaya EM and Pelling JC: Effect of extra-cellular signal-regulated kinase on p53 accumulation in response to cisplatin. J Biol Chem. 275:35778–35785. 2000. View Article : Google Scholar : PubMed/NCBI

55 

Mendoza J, Martínez J, Hernández C, Pérez-Montiel D, Castro C, Fabián-Morales E, Santibáñez M, González-Barrios R, Díaz-Chávez J, Andonegui MA, et al: Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours. Br J Cancer. 109:68–75. 2013. View Article : Google Scholar : PubMed/NCBI

56 

Kirschner K and Melton DW: Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer Res. 30:3223–3232. 2010.PubMed/NCBI

57 

Li W and Melton DW: Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance. Oncogene. 31:2412–2422. 2012. View Article : Google Scholar

58 

Andrieux LO, Fautrel A, Bessard A, Guillouzo A, Baffet G and Langouët S: GATA-1 is essential in EGF-mediated induction of nucleotide excision repair activity and ERCC1 expression through ERK2 in human hepatoma cells. Cancer Res. 67:2114–2123. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Cummings M, Higginbottom K, McGurk CJ, Wong OG, Köberle B, Oliver RT and Masters JR: XPA versus ERCC1 as chemosensitising agents to cisplatin and mitomycin C in prostate cancer cells: Role of ERCC1 in homologous recombination repair. Biochem Pharmacol. 72:166–175. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2016
Volume 48 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhou, P., Ma, L., Zhou, J., Jiang, M., Rao, E., Zhao, Y., & Guo, F. (2016). miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells. International Journal of Oncology, 48, 1737-1748. https://doi.org/10.3892/ijo.2016.3392
MLA
Zhou, P., Ma, L., Zhou, J., Jiang, M., Rao, E., Zhao, Y., Guo, F."miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells". International Journal of Oncology 48.4 (2016): 1737-1748.
Chicago
Zhou, P., Ma, L., Zhou, J., Jiang, M., Rao, E., Zhao, Y., Guo, F."miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells". International Journal of Oncology 48, no. 4 (2016): 1737-1748. https://doi.org/10.3892/ijo.2016.3392