CREB1 regulates KPNA2 by inhibiting mir-495-3p transcription to control melanoma progression

Abstract

Background Melanoma is a common type of skin cancer, and its incidence is increasing gradually. Exploring melanoma pathogenesis helps to find new treatments. Objective We aimed to explore the potential molecular mechanisms by which CREB1 regulates melanoma. Methods TransmiR and ALGGEN were used to predict targets of CREB1 in the promoter of miR-495-3p or miR-495-3p and KPNA2, and a dual-luciferase reporter assay was performed to detect binding of CREB1 to these promoters. In addition, binding of CREB1 to the miR-495-3p promoter was confirmed by a ChIP assay. qRT‒PCR was carried out to detect mRNA levels of miR-495-3p, CREB1 and KPNA2. An EdU assay was conducted to detect cell viability. Transwell assays and flow cytometry were performed to assess cell migration and invasion and apoptosis, respectively. Moreover, factors associated with overall survival were analysed by using the Cox proportional hazards model. Results Our results show miR-495-3p to be significantly decreased in melanoma. Additionally, miR-495-3p overexpression inhibited melanoma cell viability. CREB1 targeted miR-495-3p, and CREB1 overexpression enhanced melanoma cell viability by inhibiting miR-495-3p transcription. Moreover, miR-495-3p targeted KPNA2, and CREB1 regulated KPNA2 by inhibiting miR-495-3p transcription to enhance melanoma cell viability. Conclusion CREB1 regulates KPNA2 by inhibiting miR-495-3p transcription to control melanoma progression. Our results indicate the molecular mechanism by which the CREB1/miR-495-3p/KPNA2 axis regulates melanoma progression.

Matrine regulates miR‐495‐3p/miR‐543/PDK1 axis to repress the progression of acute myeloid leukemia via the Wnt/β‐catenin pathway

“…The role of miR‐495‐3p in cancers has been well‐studied. MiR‐495‐3p was involved in the progression of diffuse large B‐cell lymphoma (Yuan et al., 2022), clear cell renal cell carcinoma (Shan et al., 2022), and melanoma (Geng et al., 2022). Moreover, long noncoding RNA (lncRNA) myocardial infarction associated transcript (MIAT) negatively modulated miR‐495‐3p to boost the development of AML (Wang et al., 2019).…”