Diabetes, characterized by chronic hyperglycemia, is closely associated with worse outcomes in patients with colorectal cancer (CRC). However, the mechanism underlying the influence of high glucose levels on CRC prognosis has not yet been fully elucidated. Tribbles 3 (TRIB3) protein, a unique pseudokinase, has been implicated as an intermediary between metabolism and oncogenesis. The present study aimed to elucidate whether TRIB3 is modulated by elevated glucose levels in CRC and contributes to the malignant behavior of diabetic CRC tumors. TRIB3 expression was detected using immunohistochemistry in colon cancer tissues from patients with and without diabetes. Following the knockdown of TRIB3 by short hairpin RNA, colon cancer cell proliferation and migration were assessed using Cell Counting Kit‑8 and Transwell assays. Additionally, changes in the expression of related genes were detected using reverse transcription‑quantitative PCR, western blotting and immunofluorescence staining. The present study detected significant upregulation of TRIB3 in diabetic CRC. In addition, the findings indicated that TRIB3 may promote epithelial‑mesenchymal transition (EMT) by activating the PI3K/AKT signaling pathway, thereby enhancing the malignant characteristics of CRC. By contrast, TRIB3 knockdown in CRC cells mitigated glucose‑induced proliferation, invasiveness and EMT progression. In conclusion, TRIB3 may be modulated by increased glucose levels, subsequently contributing to the malignancy of tumor cells in diabetic CRC by modifying EMT status. These findings underscore the potential of TRIB3 as a therapeutic target for effective management of patients with diabetic and CRC.
Bai et al. (Tue,) studied this question.