Bladder cancer-associated transcript 1 promotes melanoma cell proliferation and invasion via the miR-374b-5p/U2-associated factor homology motif kinase 1 axis.

Melanoma is a malignancy derived from melanocytes and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been confirmed to be pivotal regulators in multiple types of cancer. Many lncRNAs are aberrantly expressed in tumors and perform vital functions in cancer progression. Nevertheless, the biological role of lncRNA bladder cancer-associated transcript 1 (BLACAT1) in melanoma progression remains unexplored. In this study, the collected data showed that BLACAT1 was highly expressed in melanoma. Mechanistically, miR-374b-5p bound to BLACAT1, and U2-associated factor homology motif kinase 1 (UHMK1) was a downstream target of miR-374b-5p. BLACAT1 upregulated UHMK1 expression by acting as a competing endogenous RNA for miR-374-5b. BLACAT1 deficiency resulted in the upregulation of miR-374b-5p expression and the downregulation of UHMK1 expression in melanoma cells. Moreover, BLACAT1 activated PI3K and AKT signaling by upregulating UHMK1 expression, as shown by western blotting analyses. Functionally, UHMK1 overexpression or miR-374b-5p knockdown reversed the suppressive effect of BLACAT1 depletion on melanoma cell proliferation and invasion. In conclusion, BLACAT1 promotes melanoma cell proliferation and invasion by upregulating UHMK1 expression via miR-374b-5p to activate the PI3K/AKT pathway. These results might provide promising insight into the investigation of prognostic biomarkers of melanoma.

STAT3 activates the transcription of lncRNA NR2F1-AS1 to promote the progression of melanoma via regulating the miR-493-5p/GOLM1 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are vital regulators during the biological processes of melanoma. The present study aimed to uncover biological functions of lncRNA termed NR2F1 antisense RNA 1 (NR2F1-AS1) in melanoma and the potential mechanisms. METHODS: Relative levels of NR2F1-AS1 and miR-493-5p in a total of 137 paired primary melanoma tissues and corresponding non-tumor tissues, as well as three melanoma cell lines, were examined by a real-time polymerase chain reaction. The clinical significance of NR2F1-AS1 expression was analyzed statistically. The STAT3 binding motif in the promoter region of NR2F1-AS1 was identified by JASPAR (http://jaspar.genereg.net). The association between STAT3 and NR2F1-AS1 was determined by dual-luciferase reporter and chromatin immunoprecipitation assays. The effects of NR2F1-AS1 on cell proliferation, migration and were measured by cell counting kit-8 (CCK-8), Edu, transwell and wound healing assays. Dual-luciferase reporter and RNA pull-down assays were applied to validate the interaction among NR2F1-AS1, miR-493-5p and GOLM1. Furthermore, in vivo experiments were conducted to demonstrate the oncogenic role of NR2F1-AS1 in melanoma. RESULTS: Up-regulated NR2F1-AS1 and down-regulated miR-493-5p were detected in melanoma tumors and cells. The overexpression of NR2F1-AS1 was induced by STAT3. High NR2F1-AS1 expression was correlated to advanced tumor stage and poor prognosis of melanoma. Functional studies using CCK-8, Edu, transwell and wound healing assays revealed that the proliferative, migratory and invasive capacities of melanoma cells were attenuated by the by inhibition of NR2F1-AS1. Moreover, NR2F1-AS1 was able to up-regulate GOLM1 through recognizing and binding miR-493-5p. Furthermore, knockdown of miR-493-5p distinctly reversed these inhibitory effects of NR2F1-AS1 down-regulation on the tumorigenesis and progression of melanoma. CONCLUSIONS: Our findings demonstrate a key role for NR2F1-AS1 in melanoma progression via targeting miR-493-5p/GOLM1 axis.