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Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy. | LitMetric

AI Article Synopsis

  • RNA-binding proteins (RBPs) and circular RNAs (circRNAs) play significant roles in colorectal cancer (CRC) development, with RBPs contributing to the formation of processing bodies (PBs) associated with cancer progression.
  • The study identifies MEX-3 RNA binding family member A (MEX3A) as a protein that is upregulated in CRC and correlates with poorer patient survival, mediating aggressive tumor behavior by promoting mRNA degradation through its interaction with circMPP6.
  • MEX3A and circMPP6 collaborate to regulate PB dynamics, suggesting that their interaction can serve as a prognostic marker and potential therapeutic target in CRC treatment.

Article Abstract

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987644PMC
http://dx.doi.org/10.1038/s41392-024-01787-3DOI Listing

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