Affiliation:
1. Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
2. Medical Key Laboratory of Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China
3. Zhengzhou Key Laboratory of Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
4. Branch Center of Advanced Medical Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
Abstract
N6-methyladenosine (m6A) modification plays a crucial role in determining the fate and function of RNA transcripts in tumor cells. Nevertheless, how m6A regulates the expression of key molecules and coordinates its involvement in the development of colorectal cancer (CRC) remains largely unclear. Here, we report that the m6A reading protein YTHDF1-mediated up-regulation of SH3TC2 promotes CRC growth both in vitro and in vivo. In a pan-cancer analysis across more than thirty types of cancer, we found that SH3TC2 was dysregulated in nine cancers, including BLCA, CHOL, COAD, LAML, PAAD, READ, SKCM, BRCA, and TGCT, and was closely associated with patient prognosis in four cancers, including COAD, MESO, PAAD, and READ. In particular, SH3TC2 was overexpressed in CRC as confirmed by six independent study cohorts. Clinically, high expression of SH3TC2 predicted worse disease-free survival (DFS) in CRC patients. SH3TC2 showed fascinating diagnostic value and was correlated with immunosuppression in CRC. Functionally, RNA-sequencing combined with experiments revealed that knockdown of SH3TC3 significantly inhibited cell-cycle progress of CRC, impairing cell growth. Mechanistically, YTHDF1 protein directly binds with SH3TC2 mRNA and promotes its elevation in an m6A-dependent manner. Thus, our findings provide a mechanism to target the YTHDF1/SH3TC2 axis for CRC therapy.
Funder
Medical Science and Technology Project of Henan Province
Cited by
2 articles.
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