LncRNA MSC-AS1, as an oncogene in melanoma, promotes the proliferation and glutaminolysis by regulating the miR-330-3p/ YAP1 axis.

Abstract

Melanoma is a kind of aggressive skin neoplasms with high mortality. The purpose of this present research was to investigate the effects and potential mechanisms of long-noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) in melanoma. MSC-AS1, miR-330-3p and YAP1 expression levels in melanoma tissues and cells were assessed by quantitative real-time polymerase chain reaction. Melanoma cells were evaluated using cell count kit-8, clone formation and ELISA in vitro . The relationship among MSC-AS1, YAP1 and miR-330-3p was validated by pull-down and luciferase reporter assays. Finally, the role of MSC-AS1 in vivo was determined by the xenograft model. Results showed that lncRNA MSC-AS1 was upregulated in melanoma tissues and cells. High expression of MAS-AS1 was positively correlated with a poor prognosis. Pull-down and luciferase reporter demonstrated that miR-330-3p specifically binds directly to YAP1 and MSC-AS1, respectively. MSC-AS1 promoted the expression of YAP1 by downregulating miR-330-3p. Functional experiments suggested that knockdown of MSC-AS1 suppressed the proliferation of melanoma cells and decreased the levels of glutamine, glutamate and α-ketoglutarate, glutaminase and glutamine transporter alanine-serine-cysteine transporter 2. Upregulation of miR-330-3p alleviated the promotion effect of MSC-AS1 overexpression on the proliferation and glutaminolysis of melanoma cells. The above changes could be reversed by YAP1 overexpression. In addition, knockdown of MSC-AS1 dramatically restrained the growth of melanoma cells in xenograft model. In conclusion, our results revealed that MSC-AS1 facilitated the proliferation and glutaminolysis of melanoma cells by regulating miR-330-3p/ YAP1 pathway, suggesting that MSC-AS1 could provide a new idea for the treatment of melanoma.