NSUN2/ALYREF-mediated RNA m5c modification promotes anoikis resistance of prostate cancer through activating autophagy.

Prostate cancer is the most common malignant tumor among men worldwide, severely threatening the health of aging males. RNA 5-methylcytosine (m5C) modification has been demonstrated to play a significant role in the initiation and progression of various tumors. However, the role of ALYREF, a key methyl-recognizing protein for m5c modification, is still unclear in prostate cancer. In our study, we found that knockdown of ALYREF reduces the proliferation, invasion and metastasis of prostate cancer. ALYREF promotes anoikis resistance in prostate cancer by positively regulating BPIP3 and thereby activating autophagy. Mechanistically, we found that ALYREF is a methylation recognition protein that directly and specifically recognizes the m5c site of BNIP3 mRNA and enhances the stability of BNIP3 mRNA, which activates autophagy in prostate cancer cells, and thus enhances the anoikis resistance and metastatic ability of cancer cells. Overall, our study revealed the important role of ALYREF-mediated m5C methylation modification in the mechanisms of autophagy and anoikis resistance in prostate cancer, providing an important molecular target for the treatment of advanced prostate cancer.