NSUN2/ALYREF-mediated RNA m5c modification promotes anoikis resistance of prostate cancer through activating
Guangyu Sun1, Shuaiqi Chen2, Mingzhe Chen1
1Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.
Abstract:
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.
Insights
This study reveals that ALYREF protein promotes prostate cancer progression by enhancing anoikis resistance and metastasis through m5C modification of BNIP3 mRNA, identifying it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Prostate cancer is a leading global health concern for aging men.
- RNA 5-methylcytosine (m5C) modification is implicated in various cancers.
- The function of ALYREF in prostate cancer remains largely unknown.
Purpose of the Study:
- To investigate the role of ALYREF in prostate cancer.
- To elucidate the mechanism by which ALYREF influences cancer progression.
- To identify ALYREF as a potential therapeutic target for advanced prostate cancer.
Main Methods:
- Knockdown of ALYREF in prostate cancer cells.
- Analysis of proliferation, invasion, and metastasis.
- Investigation of anoikis resistance and autophagy.
- Identification of ALYREF binding to BNIP3 mRNA m5C site.
Main Results:
- Knockdown of ALYREF significantly reduced prostate cancer proliferation, invasion, and metastasis.
- ALYREF enhances anoikis resistance by upregulating BNIP3 and activating autophagy.
- ALYREF directly binds to the m5C site of BNIP3 mRNA, increasing its stability.
- This mechanism enhances prostate cancer cell survival and metastatic potential.
Conclusions:
- ALYREF plays a crucial role in prostate cancer progression.
- ALYREF-mediated m5C modification of BNIP3 mRNA is key to autophagy and anoikis resistance.
- ALYREF represents a promising molecular target for advanced prostate cancer treatment.
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