ALKBH5 Inhibits Cancer Cell Proliferation in Prostate Cancer through KLF4/TERT Signaling

N6-methyladenosine (m(6)A), as a reversible chemical modification of RNA, is a new type of posttranscriptional gene regulation, which plays an important role in cell differentiation and tumorigenesis, and is also a research hotspot in epigenetic transcriptomics in recent years. The purpose of this study was to discuss the action mechanism of m(6)A demethylase ALKBH5 in the occurrence of prostate cancer (PCa). We found that ALKBH5 was lowly expressed in PCa, and the decreased expression of ALKBH5 was responsible for the poor prognosis of prostate carcinomas. Moreover, ALKBH5 downregulated the expression of Kruppel-like factor 4 (KLF4) by reducing its mRNA stability, which reduced the transcriptional activity of KLF4 on the downstream target telomerase reverse transcriptase (TERT) and decreased TERT expression and telomerase activity, eventually inhibiting PCa cell growth. The findings of this study reveal the action mechanism of ALKBH5 in PCa from the perspective of epitranscriptomics, which would provide new ideas for the prevention of PCa.

Automated summary

This study explores the action mechanism of m(6)A demethylase ALKBH5 in the occurrence of prostate cancer. It was found that ALKBH5 is lowly expressed in prostate cancer, and its decreased expression is associated with poor prognosis. Additionally, ALKBH5 downregulates the expression of KLF4 by reducing its mRNA stability, which leads to decreased expression and activity of TERT, ultimately inhibiting prostate cancer cell growth. The findings of this study provide new insights for the prevention of prostate cancer from the perspective of epitranscriptomics.