Background: Colorectal cancer (CRC) stands as the second most prevalent cause of cancer-related mortality globally, while its incidence holds the third position among newly diagnosed cancer cases worldwide. Colorectal carcinogenesis is complicated, and the processes are triggered by the complex interaction of some genetic and environmental factors, including DNA methylation. Previous studies showed that RALYL is hypermethylated in CRC. We aimed to explore the role of RALYL in CRC involved in MNK2 alternative splicing in the present study.
Methods: Bioinformatics analysis, detection in CRC samples, and experiments in vitro and in vivo combined with gene knockdown and overexpression were conducted. Cell proliferation and tumor growth assays were performed.
Results: Results showed that hypermethylated RALYL is lowly expressed in CRC. Overexpression of RALYL suppresses cell proliferation in vitro and tumor growth in vivo in CRC. MNK2 alternative splicing is essential for the tumor suppressive role of RALYL, along with RALYL regulating MNK2 alternative splicing via HNRNPC in CRC.
Conclusions: RALYL potentially exerts an inhibitory effect on CRC by engaging with HNRNPC to orchestrate the alternative splicing of MNK2. RALYL binds to HNRNPC to promote MNK2 splicing into MNK2a instead of MNK2b, consequently activating the p38 MAPK signaling pathway and inhibiting tumor proliferation in CRC. Our findings suggest that RALYL might suppress CRC through binding to HNRNPC to promote MNK2 splicing toward MNK2a, thereby activating the p38 MAPK signaling cascade.
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| http://dx.doi.org/10.1002/cnr2.70179 | DOI Listing |
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