Knockdown of BUB1B Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer by Regulating the JNK/c-Jun Signaling Pathway.

Abstract

Listen

Translate article

Background: Colorectal cancer (CRC) ranks as the third most common cancer, accounting for a significant number of cancer-related deaths worldwide every year. Yet, the molecular mechanisms responsible for the progression of this malignancy are not fully understood. Numerous studies indicate that BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) plays a role in the progression of various malignant tumors. However, the specific biological functions and the detailed mechanisms of how BUB1B influences CRC are still not completely known. This study aimed to explore the expression and role of BUB1B in CRC. Materials and Methods: To achieve this, the expression levels of BUB1B in human CRC tissues and cell lines were examined using real-time polymerase chain reaction and Western blotting. The role and associated mechanisms of BUB1B in CRC cell progression were assessed both in vitro and in vivo using RNA interference. Results: The findings of this study revealed an elevated expression of BUB1B in both CRC tissues and cell lines. The silencing of BUB1B in CRC cell lines notably inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest and apoptosis. In addition, the knockdown of BUB1B inhibited the JNK/c-Jun signaling pathway, increased the expression of proapoptotic proteins, and decreased the expression of antiapoptotic proteins. The effects of BUB1B knockdown on CRC cell progression were reversed by the JNK activator PAF(C-16). Conclusions: In summary, the suppression of BUB1B hindered malignant tumor progression and heightened apoptosis and cell cycle arrest in CRC cells via the JNK/c-Jun pathway. Importantly, the removal of BUB1B expression curtailed tumor growth in human CRC xenografts in nude mice, suggesting its potential as a promising therapeutic target for CRC patients. ClinicalTrials.gov ID: No.2019 K-C086.