RNA-binding protein MEX3A controls G1/S transition via regulating the RB/E2F pathway in clear cell renal cell...

Area of Science:

• Molecular Biology
• Oncology
• Cancer Research

Background:

• MEX3A is an RNA-binding protein involved in mRNA decay.
• Its specific role and mechanism in clear cell renal cell carcinoma (ccRCC) were previously unknown.

Purpose of the Study:

• To investigate the function and mechanism of MEX3A in ccRCC.
• To identify MEX3A's downstream targets and regulatory pathways in ccRCC.

Main Methods:

• Quantitative real-time PCR and Western blotting to assess MEX3A expression.
• Cell proliferation assays (in vitro and in vivo) and cell cycle analysis.
• Enhanced cross-linking and immunoprecipitation sequencing (eCLIP-seq) and RNA-immunoprecipitation sequencing (RIP-seq) to identify MEX3A targets.
• Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis.
• Luciferase reporter assays and rescue experiments to validate target interactions.

Main Results:

• MEX3A expression is upregulated in ccRCC, transcriptionally activated by ETS1.
• Silencing MEX3A inhibits ccRCC cell proliferation and induces G1/S cell cycle arrest.
• MEX3A directly binds to the 3' UTR of CDKN2B mRNA, promoting its degradation and reducing CDKN2B levels.
• eCLIP-seq and RIP-seq identified a network of approximately 4,000 potential MEX3A target genes.
• GO analysis revealed enrichment of negative regulation of cell proliferation pathways among MEX3A-bound genes.

Conclusions:

• MEX3A functions as a post-transcriptional regulator promoting abnormal cell cycle progression in ccRCC.
• MEX3A contributes to ccRCC development by downregulating CDKN2B, leading to cell cycle dysregulation.
• Targeting MEX3A may represent a potential therapeutic strategy for ccRCC.