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

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.

RETRACTED: CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

“…Furthermore, reducing the miR‐637 level was sufficient to reverse shcircEPHB4‐induced phenotypes. Studies in other cancers have established miR‐637 as a consistent tumor suppressor [16–18]. In gliomas, Que et al .…”

microRNA‐637 promotes apoptosis and suppresses proliferation and autophagy in multiple myeloma cell lines via NUPR1

“…The result is in accordance with the previous report exhibiting that overexpression of miR-637 inhibited proliferation and induced apoptosis [19].…”

“…In the present study, the overexpression of miR-637 in MM cells caused a significant reduction in proliferation and autophagy but a promotion in apoptosis, showing a tumor-suppressive role in MM. The result is in accordance with the previous report exhibiting that the overexpression of miR-637 inhibited proliferation and induced apoptosis [17]. In this study, the expression level of miR-637 was first explored in 36 human samples, and it was found that the expression of miR-637 in the bone marrow The cell viability of MM cells after transfecting miR-637 mimics, NC-LV, or NUPR1-LV was determined by CCK-8 assay.…”

Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

“…Moreover, supporting our previous results, miR-637 was found to target Akt1 and hamper tumorigenesis in both thyroid carcinoma and pancreatic ductal adenocarcinoma (35,36). MiR-637 could also inhibit Akt phosphorylation and promote melanoma progression (37). Remarkably, although several circular RNAs or long non-coding RNAs (lncRNAs) were found to regulate miR-637 through the mechanism of competitive endogenous RNA, few studies have investigated the crosstalk between transcription factors and miR-637.…”