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Vol. 64 No. 11: Issue 11

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MiR-637 suppresses melanoma progression through directly targeting P-REX2a and inhibiting PTEN/AKT signaling pathway

https://doi.org/10.14715/cmb/2018.64.11.10
Jian Zhang
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Wen-Li Liu
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Lu Zhang
Department of Foreign Languages, Ming De College of Northwestern Polytechnical University, Xi'an 710124, Shaanxi Province, P.R. China
Rui Ge
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Fang He
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Tian-Yuan Gao
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Qiong Tian
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Xin Mu
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Li-Hong Chen
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Wei Chen
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China
Xu Li
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, P.R. China

Corresponding Author(s) : Xu Li

lixu_xjtu@163.com

Cellular and Molecular Biology, Vol. 64 No. 11: Issue 11

Abstract

MicroRNAs (miRNAs) play important roles in melanoma. Although miR-637 has been suggested to be a tumor suppressor in several cancers, its function in melanoma and the molecular mechanism behind that function remain unclear. In this study, we investigated the role of miR-637 in human melanoma and explored its relevant mechanisms. We found that the expression of miR-637 is significantly downregulated in melanoma tissues and cell lines. While overexpression of miR-637 inhibited melanoma cell proliferation and cell cycle G1-S transition, and induced apoptosis. Inhibition of miR-637 promoted cell proliferation and G1-S transition, and suppressed apoptosis. Subsequent investigation revealed that miR-637 expression was inversely correlated with P-REX2a expression in melanoma tissues. P-REX2a was determined to be a direct target of miR-637 by using a luciferase reporter assay. Overexpression of miR-637 decreased P-REX2a expression at both the mRNA and protein levels, and suppression of miR-637 increased P-REX2a expression. Importantly, silencing P-REX2a recapitulated the cellular and molecular effects seen upon miR-637 overexpression, whereas, overexpression of P-REX2a eliminated the effects of miR-637 overexpression on melanoma cells. Furthermore, both enforced expression of miR-637 or silencing of P-REX2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Taken together, our study demonstrates that miR-637 inhibites melanoma cell proliferation by activation of AKT signaling pathway and induces apoptosis through regulation of Bcl-2/Bax expression via targeting P-REX2a. These findings suggest that miR-637 plays a crucial role in melanoma progression, and may serve as a potential novel target for melanoma therapy.

Keywords

miR-637 Melanoma P-REX2a Proliferation Apoptosis.
Zhang, J., Liu, W.-L., Zhang, L., Ge, R., He, F., Gao, T.-Y., Tian, Q., Mu, X., Chen, L.-H., Chen, W., & Li, X. (2018). MiR-637 suppresses melanoma progression through directly targeting P-REX2a and inhibiting PTEN/AKT signaling pathway. Cellular and Molecular Biology, 64(11), 50–57. https://doi.org/10.14715/cmb/2018.64.11.10
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