CSDE1 regulates the miR-20a-5p/TMBIM6 axis in melanoma.

RNA-binding proteins (RBPs) and microRNAs (miRNAs) play crucial roles in regulating gene expression at the post-transcriptional level in tumorigenesis. They primarily target the 3'UTRs of mRNAs to control their translation and stability. However, their coregulatory effects on specific mRNAs in the pathogenesis of particular cancers are yet to be fully explored. CSDE1 is an RBP that promotes melanoma metastasis, and the mechanisms underlying its function in melanoma development are yet to be fully understood. Here, we report that CSDE1 enhances TMBIM6 protein expression without altering its mRNA levels in melanoma cells, indicating post-transcriptional regulation. CSDE1 and AGO2 competitively bind to TMBIM6 mRNA, and we identify that miR-20-5p, which represses TMBIM6 expression, regulates the binding of CSDE1 to TMBIM6 mRNA. Further, the RNA-binding mutant of CSDE1 showed reduced affinity toward TMBIM6 mRNA, thus allowing AGO2-mediated silencing of TMBIM6 expression. Our study highlights the pivotal role of CSDE1 in regulating miR-20a-5p function and the expression of TMBIM6 in melanoma cells, thus unveiling the potential of therapeutic strategies targeting this regulatory pathway in treating malignant skin cancers.