CKMT1B regulates the proliferation, migration, invasion, and apoptosis of colorectal cancer cells through the AKT/mTOR/STAT3 pathway.

Abstract

This study aimed to investigate the role of CKMT1B in the growth, migration, invasion, and apoptosis of colorectal cancer (CRC) cells, focusing on its regulation of the AKT/mTOR/STAT3 signaling pathway. Bioinformatics analysis indicated that the CK family expression exhibited heterogeneity and correlation across various cancers, with CKMT1B significantly underexpressed in CRC, suggesting its potential role as a tumor suppressor gene. Additionally, reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were employed to evaluate CKMT1B expression in CRC cell lines. To assess the effects of CKMT1B knockdown and overexpression in LOVO cells, CCK-8, plate cloning, scratch, Transwell chamber, and Muse assays were used to measure cell proliferation, migration, invasion, and apoptosis. The regulatory mechanism of CKMT1B in CRC was further explored through the AKT/mTOR/STAT3 pathway and related proteins. Downregulation of CKMT1B enhanced the proliferation, migration, and invasion of LOVO cells while inhibiting apoptosis, while CKMT1B overexpression had the opposite effect. Moreover, CKMT1B overexpression led to a decrease in the anti-apoptotic protein BCL2 and an increase in the tumor suppressor protein p53, suggesting its role in modulating apoptotic pathways. The expression levels of the pathway-related proteins P-AKT, P-mTOR, and P-STAT3 were significantly reduced, suggesting that CKMT1B regulates the AKT/mTOR/STAT3 signaling pathway, thereby modulating CRC progression. Taken together, these findings suggest that CKMT1B could serve as a promising molecular target for CRC treatment.