Long noncoding RNA MHENCR promotes melanoma progression via regulating miR-425/489-mediated PI3K-Akt pathway.

Abstract

Increasing evidences demonstrated that long noncoding RNAs (lncRNAs) are frequently dysregulated and have critical roles in many tumors. However, the roles and functional mechanisms of lncRNAs in melanoma remain largely unknown. In this study, we identified a novel lncRNA MHENCR which was upregulated in melanoma tissues and further upregulated in metastatic melanoma. Increased expression of MHENCR indicted poor survival of melanoma patients. Functional experiments revealed that MHENCR knockdown significantly inhibited melanoma cells proliferation, induced cell cycle arrest and apoptosis, and also attenuated melanoma cells migration <i>in vitro</i>. Furthermore, we identified MHENCR as a competitively endogenous RNA, which specifically bound to miR-425 and miR-489, upregulated their target genes IGF1 and SPIN1 expression, and further activated PI3K-Akt pathway. Statistically significant correlations were observed between MHENCR expression and IGF1 and SPIN1 in melanoma tissues. <i>In vivo</i> functional experiments further confirmed the pro-growth and pro-metastasis roles of MHENCR. Collectively, our findings revealed that MHENCR functions as an oncogene in melanoma via activating miR-425/489-mediated PI3K-Akt pathway, and may be a therapeutic target for melanoma.