Long noncoding RNA ZFAS1 promotes tumorigenesis through regulation of miR-150-5p/RAB9A in melanoma

Abstract

Melanoma is the deadliest form of skin cancer and one of the most aggressive cancers. ZFAS1 is a newly identified lncRNA, playing an oncogenic role in several types of cancer. The present study aimed to investigate the function and mechanism of ZFAS1-induced regulation of melanoma. ZFAS1 expression was increased in melanoma tissues and cells compared with normal controls. ZFAS1 expression in metastatic tissues was higher than that in nonmetastatic subjects. Higher expression of ZFAS1 predicted lower survival rates. Knockdown of ZFAS1 decreased proliferation, increased apoptosis, decreased migration and invasion, and reduced epithelial–mesenchymal transition potential in melanoma cells. Moreover, ZFAS1 knockdown inhibited tumor growth in nude mice. There was a direct binding between ZFAS1 and miR-150-5p. ZFAS1 negatively regulated miR-150-5p expression and upregulation of miR-150-5p was involved in ZFAS1 knockdown-induced effect on proliferation, apoptosis, migration, and invasion. Using bioinformatics, we predicted the binding between RAB9A and miR-150-5p, and the direct interaction between RAB9A and miR-150-5p was confirmed by luciferase reporter and RNA immunoprecipitation assays. We also showed that RAB9A expression was regulated negatively by miR-150-5p, but was regulated positively by ZFAS1. Downregulation of RAB9A significantly inhibited the increase in proliferation, decrease in apoptosis, and increase in migration and invasion induced by miR-150-5p inhibitors. Moreover, RAB9A knockdown decreased proliferation, increased apoptosis, and decreased migration and invasion in melanoma cells. In summary, we confirmed the tumor-promoting role of ZFAS1 in melanoma and provide evidence for the role and mechanism of the ZFAS1/miR-150-5p/RAB9A axis. These findings may lead to novel therapeutic strategies for melanoma.