Open Access

miR‑186 suppressed CYLD expression and promoted cell proliferation in human melanoma

  • Authors:
    • Haijiang Qiu
    • Suirong Yuan
    • Xiaohe Lu
  • View Affiliations

  • Published online on: August 11, 2016     https://doi.org/10.3892/ol.2016.5002
  • Pages: 2301-2306
  • Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have shown that microRNA‑186 (miR‑186) is overexpressed in various human cancers and is associated with the regulation of the carcinogenic processes. However, the underlying mechanisms of this microRNA in melanoma remain largely unknown. In the present study, the overexpression of miR‑186 was identified in melanoma tissues and melanoma cells compared to the expression of miR‑186 in the matched tumor adjacent tissues and normal human epidermal melanocytes. Overexpression of miR‑186 promoted the proliferation and anchorage‑independent growth of melanoma cells, whereas inhibition of miR‑186 reduced this effect. Bioinformatics analysis also revealed cylindromatosis (CYLD), a putative tumor suppressor, to be a potential target of miR‑186. Luciferase reporter assays showed that miR‑186 directly targeted the 3'‑untranslated regions of CYLD messenger RNA. Additional experiments showed that overexpression of miR‑186 promoted the proliferation of melanoma cells, which was consistent with the inhibitory effects induced by knockdown of CYLD. In summary, the present study indicated that miRNA‑186 plays a crucial role in melanoma growth and its oncogenic effect is mediated chiefly through the direct suppression of CYLD expression.

References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Baroudjian B, Pagès C and Lebbé C: Melanoma, from diagnosis to treatment. Rev Infirm. 65:16–18. 2016. View Article : Google Scholar

3 

Luo C, Weber CE, Osen W, Bosserhoff AK and Eichmuller SB: The role of microRNAs in melanoma. Eur J Cell Biol. 93:11–22. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Mimeault M and Batra SK: Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas. World J Clin Oncol. 3:32–42. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Cui G, Cui M, Li Y, Liang Y, Li W, Guo H and Zhao S: MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells. Tumour Biol. 35:8933–8937. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Kim SY, Lee YH and Bae YS: MiR-186, miR-216b, miR-337-3p and miR-760 cooperatively induce cellular senescence by targeting α subunit of protein kinase CKII in human colorectal cancer cells. Biochem Biophys Res Commun. 429:173–179. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Cai J, Wu J, Zhang H, Fang L, Huang Y, Yang Y, Zhu X, Li R and Li M: miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 73:756–766. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Ries J, Vairaktaris E, Agaimy A, Kintopp R, Baran C, Neukam FW and Nkenke E: miR-186, miR-3651 and miR-494: Potential biomarkers for oral squamous cell carcinoma extracted from whole blood. Oncol Rep. 31:1429–1436. 2014.PubMed/NCBI

11 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Mathis BJ, Lai Y, Qu C, Janicki JS and Cui T: CYLD-mediated signaling and diseases. Curr Drug Targets. 16:284–294. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Zhong Q, Wang T, Lu P, Zhang R, Zou J and Yuan S: miR-193b promotes cell proliferation by targeting Smad3 in human glioma. J Neurosci Res. 92:619–626. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Shi L, Wang Z, Sun G, Wan Y, Guo J and Fu X: miR-145 inhibits migration and invasion of glioma stem cells by targeting ABCG2. Neuromolecular Med. 16:517–528. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Wang HF, Chen H, Ma MW, Wang JA, Tang TT, Ni LS, Yu JL, Li YZ and Bai BX: miR-573 regulates melanoma progression by targeting the melanoma cell adhesion molecule. Oncol Rep. 30:520–526. 2013.PubMed/NCBI

17 

Prasad R and Katiyar SK: Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein. Oncotarget. 5:10636–10649. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Liu SM, Lu J, Lee HC, Chung FH and Ma N: miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2. Oncotarget. 5:9444–9459. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Babapoor S, Fleming E, Wu R and Dadras SS: A novel miR-451a isomiR, associated with amelanotypic phenotype, acts as a tumor suppressor in melanoma by retarding cell migration and invasion. PLoS One. 9:e1075022014. View Article : Google Scholar : PubMed/NCBI

20 

Rico-Rosillo MG, Vega-Robledo GB and Oliva-Rico D: The role and importance of the microRNAs in the diagnosis and development of diseases. Rev Med Inst Mex Seguro Soc. 52:302–307. 2014.(In Spanish). PubMed/NCBI

21 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Deng LL, Shao YX, Lv HF, Deng HB and Lv FZ: Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells. Neoplasma. 59:18–29. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Massoumi R: CYLD: A deubiquitination enzyme with multiple roles in cancer. Future Oncol. 7:285–297. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Lim JH, Jono H, Komatsu K, Woo CH, Lee J, Miyata M, Matsuno T, Xu X, Huang Y, Zhang W, et al: CYLD negatively regulates transforming growth factor-β-signalling via deubiquitinating Akt. Nat Commun. 3:7712012. View Article : Google Scholar : PubMed/NCBI

25 

Blake PW and Toro JR: Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: Novel insights into the role of deubiquitination in cell signaling. Hum Mutat. 30:1025–1036. 2009. View Article : Google Scholar : PubMed/NCBI

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October 2016
Volume 12 Issue 4

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Copy and paste a formatted citation
APA
Qiu, H., Yuan, S., & Lu, X. (2016). miR‑186 suppressed CYLD expression and promoted cell proliferation in human melanoma. Oncology Letters, 12, 2301-2306. https://doi.org/10.3892/ol.2016.5002
MLA
Qiu, H., Yuan, S., Lu, X."miR‑186 suppressed CYLD expression and promoted cell proliferation in human melanoma". Oncology Letters 12.4 (2016): 2301-2306.
Chicago
Qiu, H., Yuan, S., Lu, X."miR‑186 suppressed CYLD expression and promoted cell proliferation in human melanoma". Oncology Letters 12, no. 4 (2016): 2301-2306. https://doi.org/10.3892/ol.2016.5002