MicroRNA‑24‑1‑5p promotes malignant melanoma cell autophagy and apoptosis via regulating ubiquitin D.

The present study aimed to investigate the key roles and possible regulatory mechanism of microRNA (miR)‑24‑1‑5p in regulating the autophagy, and apoptosis of malignant melanoma cells. The expression levels of miR‑24‑1‑5p in malignant melanoma tissues were determined. Human melanoma A375 cells were transfected with miR‑24‑1‑5p mimic and control. The effects of miR‑24‑1‑5p overexpression on regulating the expressions of autophagy‑related proteins [microtubule‑associated protein 1A/1B‑light chain 3 (LC3)‑II, LC3‑I and Beclin‑1] and apoptosis‑related proteins [apoptosis regulator Bcl‑2 (Bcl‑2) and (BCL2 like 1) Bcl‑xL] were investigated. The percentage of apoptotic cells in different transfected cells was detected. In addition, luciferase reporter assays were performed to confirm whether ubiquitin D (UBD) was a target of miR‑24‑1‑5p. The effects of UBD silencing on autophagy and apoptosis were also investigated. The expression levels of janus kinase (JNK), phosphorylated (P)‑JNK, Jun proto‑oncogene AP‑1 transcription factor subunit (c‑Jun) and p‑c‑Jun were determined following the overexpression of miR‑24‑1‑5p, and UBD. In comparison with adjacent normal tissues, miR‑24‑1‑5p was significantly downregulated in malignant melanoma tissues. Overexpression of miR‑24‑1‑5p significantly increased the levels of LC3‑II/I ratio and Beclin‑1 expression, and decreased the expression levels of Bcl‑2 and Bcl‑xL. Flow cytometry also showed that miR‑24‑1‑5p overexpression promoted cell apoptosis. Moreover, UBD was confirmed as a direct target of miR‑24‑1‑5p. Silencing of UBD promoted melanoma cell autophagy and apoptosis via regulating the expression levels of related proteins. Besides, the levels of the p‑JNK/JNK and p‑c‑Jun/Jun ratios were significantly increased following miR‑24‑1‑5p overexpression, which were reversed following co‑overexpression of miR‑24‑1‑5p, and UBD. Overexpression of miR‑24‑1‑5p may target UBD, and subsequently promote the autophagy and apoptosis of malignant melanoma cells through activation of the JNK signaling pathway.