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International Journal of Molecular Medicine
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Article

MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway

  • Authors:
    • Fang Wang
    • Lin Li
    • Zhuo Chen
    • Mingzhi Zhu
    • Yuanting Gu
  • View Affiliations / Copyright

    Affiliations: The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
  • Pages: 1421-1428
    |
    Published online on: March 7, 2016
       https://doi.org/10.3892/ijmm.2016.2518
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Abstract

Breast cancer ranks as the leading cause of cancer-related mortality in females worldwide. It has been proven that microRNAs (miRNAs or miRs), a type of non‑coding RNA, are involved in tumorigenesis. An increasing number of studies has confirmed the critical role of miR‑214 in certain types of cancer. Nevertheless, the biological function of miR‑214, as well as its underlying mechanisms of action in breast cancer remain largely unknown. In the present study, the expression of miR‑214 was found to be upregulated in four human breast cancer cell lines in contrast to its expression level in the non‑malignant breast epithelial cell line, MCF‑10A. Moreover, the overexpression of miR‑214 markedly increased cell viability and abrogated the apoptosis triggered by serum starvation, indicating that miR‑214 plays a pivotal role in breast cancer cell growth. Further analysis suggested that the upregulation of miR‑214 markedly induced the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, which largely accounted for the protective effects of miR‑124 on cancer cell growth. This was further confimed by pre‑treatment with the PI3K/Akt inhibitor, LY294002, which markedly attenuated the miR‑214‑induced increase in cell viability and resistance to apoptosis. Furthermore, the expression of phosphatase and tensin homolog (PTEN) was decreased following transfection wtih miR‑214 mimics and PTEN was confirmed as the direct target of miR‑214 by bioinformatics analysis and a dual‑firefly luciferase reporter assay. Importantly, the introduction of PTEN cDNA lacking the 3' untranslated region (3'UTR) significantly inhibited the miR‑214‑induced activation of the PI3K/Akt signaling pathway, and abrogated the protetive effects of miR‑214 on cell survival and resistance to apoptosis. Taken together, these findings suggest that miR‑214 possesses oncogenic activity and that its effects are mediated through the promotion of cell growth by targeting the PTEN‑PI3K/Akt pathway. Thus, pharmaceutical interventions targeting miR‑124 may provide a promising therapeutic strategy for the treatment of breast cancer.
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View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Benson JR and Jatoi I: The global breast cancer burden. Future Oncol. 8:697–702. 2012. View Article : Google Scholar : PubMed/NCBI

3 

van Rooij E and Olson EN: MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 11:860–872. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Dai R and Ahmed SA: MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res. 157:163–179. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Huang J, Lyu H, Wang J and Liu B: MicroRNA regulation and therapeutic targeting of survivin in cancer. Am J Cancer Res. 5:20–31. 2015.PubMed/NCBI

6 

Cheng H, Zhang L, Cogdell DE, Zheng H, Schetter AJ, Nykter M, Harris CC, Chen K, Hamilton SR and Zhang W: Circulating plasma miR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One. 6:e177452011. View Article : Google Scholar : PubMed/NCBI

7 

Fornari F, Milazzo M, Chieco P, Negrini M, Marasco E, Capranico G, Mantovani V, Marinello J, Sabbioni S, Callegari E, 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. 227:275–285. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Penna E, Orso F, Cimino D, Tenaglia E, Lembo A, Quaglino E, Poliseno L, Haimovic A, Osella-Abate S, De Pittà C, et al: microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. EMBO J. 30:1990–2007. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Yamada Y, Hidaka H, Seki N, Yoshino H, Yamasaki T, Itesako T, Nakagawa M and Enokida H: Tumor-suppressive microRNA-135a inhibits cancer cell proliferation by targeting the c-MYC oncogene in renal cell carcinoma. Cancer Sci. 104:304–312. 2013. View Article : Google Scholar

10 

Shih TC, Tien YJ, Wen CJ, Yeh TS, Yu MC, Huang CH, Lee YS, Yen TC and Hsieh SY: MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma. J Hepatol. 57:584–591. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Wang Z and Cai H, Lin L, Tang M and Cai H: Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Pediatr Blood Cancer. 61:206–210. 2014. View Article : Google Scholar

12 

Wang J, Li J, Wang X, Zheng C and Ma W: Downregulation of microRNA-214 and overexpression of FGFR-1 contribute to hepatocellular carcinoma metastasis. Biochem Biophys Res Commun. 439:47–53. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Schwarzenbach H, Milde-Langosch K, Steinbach B, Müller V and Pantel K: Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res Treat. 134:933–941. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Li B, Han Q, Zhu Y, Yu Y, Wang J and Jiang X: Down-regulation of miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist. FEBS J. 279:2393–2398. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Moon S-H, Kim D-K, Cha Y, Jeon I, Song J and Park K-S: PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line. Int J Oncol. 42:921–928. 2013.PubMed/NCBI

17 

Abdulaziz S, Al-Shahid M and Al-Thenayan E: A 49-year-old man with acute pulmonary hypertension post lung transplantation. Chest. 144:704–707. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Baumjohann D, Kageyama R, Clingan JM, Morar MM, Patel S, de Kouchkovsky D, Bannard O, Bluestone JA, Matloubian M, Ansel KM and Jeker LT: The microRNA cluster MIR-17~92 promotes TFH cell differentiation and represses subset-inappropriate gene expression. Nat Immunol. 14:840–848. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Zhou Y, Xiong M, Niu J, Sun Q, Su W, Zen K, Dai C and Yang J: Secreted fibroblast-derived miR-34a induces tubular cell apoptosis in fibrotic kidney. J Cell Sci. 127:4494–4506. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Zha R, Guo W, Zhang Z, Qiu Z, Wang Q, Ding J, Huang S, Chen T, Gu J, Yao M and He X: Genome-wide screening identified that miR-134 acts as a metastasis suppressor by targeting integrin β1 in hepatocellular carcinoma. PLoS One. 9:e876652014. View Article : Google Scholar

21 

Yau WL, Lam CSC, Ng L, Chow AK, Chan ST, Chan JY, Wo JY, Ng KT, Man K, Poon RT and Pang RW: Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process. PLoS One. 8:e578822013. View Article : Google Scholar : PubMed/NCBI

22 

Josson S, Gururajan M, Hu P, Shao C, Chu GY, Zhau HE, Liu C, Lao K, Lu CL, Lu YT, et al: miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer. Clin Cancer Res. 20:4636–4646. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Slomovitz BM and Coleman RL: The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 18:5856–5864. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Yulyana Y, Ho IA, Sia KC, Newman JP, Toh XY, Endaya BB, Chan JK, Gnecchi M, Huynh H, Chung AY, et al: Paracrine factors of human fetal MSCs inhibit liver cancer growth through reduced activation of IGF-1R/PI3K/Akt signaling. Mol Ther. 23:746–756. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Vo BT, Morton D Jr, Komaragiri S, Millena AC, Leath C and Khan SA: TGF-β effects on prostate cancer cell migration and invasion are mediated by PGE2 through activation of PI3K/AKT/mTOR pathway. Endocrinology. 154:1768–1779. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S and Arteaga CL: Herceptin-induced inhibition of phosphati-dylinositol-3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res. 62:4132–4141. 2002.PubMed/NCBI

27 

Kumar P, Miller AI and Polverini PJ: p38 MAPK mediates γ-irradiation-induced endothelial cell apoptosis, and vascular endothelial growth factor protects endothelial cells through the phosphoinositide 3-kinase-Akt-Bcl-2 pathway. J Biol Chem. 279:43352–43360. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Song MS, Salmena L and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 13:283–296. 2012.PubMed/NCBI

29 

Mulholland DJ, Tran LM, Li Y, Cai H, Morim A, Wang S, Plaisier S, Garraway IP, Huang J, Graeber TG and Wu H: Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell. 19:792–804. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Lee S, Choi EJ, Jin C and Kim DH: Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 97:26–34. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang F, Li L, Chen Z, Zhu M and Gu Y: MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med 37: 1421-1428, 2016.
APA
Wang, F., Li, L., Chen, Z., Zhu, M., & Gu, Y. (2016). MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. International Journal of Molecular Medicine, 37, 1421-1428. https://doi.org/10.3892/ijmm.2016.2518
MLA
Wang, F., Li, L., Chen, Z., Zhu, M., Gu, Y."MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway". International Journal of Molecular Medicine 37.5 (2016): 1421-1428.
Chicago
Wang, F., Li, L., Chen, Z., Zhu, M., Gu, Y."MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway". International Journal of Molecular Medicine 37, no. 5 (2016): 1421-1428. https://doi.org/10.3892/ijmm.2016.2518
Copy and paste a formatted citation
x
Spandidos Publications style
Wang F, Li L, Chen Z, Zhu M and Gu Y: MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med 37: 1421-1428, 2016.
APA
Wang, F., Li, L., Chen, Z., Zhu, M., & Gu, Y. (2016). MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. International Journal of Molecular Medicine, 37, 1421-1428. https://doi.org/10.3892/ijmm.2016.2518
MLA
Wang, F., Li, L., Chen, Z., Zhu, M., Gu, Y."MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway". International Journal of Molecular Medicine 37.5 (2016): 1421-1428.
Chicago
Wang, F., Li, L., Chen, Z., Zhu, M., Gu, Y."MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway". International Journal of Molecular Medicine 37, no. 5 (2016): 1421-1428. https://doi.org/10.3892/ijmm.2016.2518
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