![]() 1 Successive accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) contribute to the tumorigenesis of CRC. Altogether, our results reveal the tumor-suppressive role of TBX20 by inhibiting NHEJ-mediated DNA repair in CRC cells, and provide a potential biomarker for predicting the prognosis of patients with early-stage CRC and a therapeutic target for combination therapy.Ĭolorectal carcinoma (CRC) ranks third in terms of incidence, and second in terms of mortality worldwide, accounting for ~10% of cancer-related deaths. Furthermore, we revealed that TBX20 suppressed cell proliferation and tumor growth through impairing non-homologous DNA end joining (NHEJ)-mediated double-stranded break repair by binding the middle domain of both Ku70 and Ku80 and therefore inhibiting their recruitment on chromatin in CRC cells. Moreover, we identified PDZRN3 as the E3 ubiquitin ligase of TBX20 protein, which mediated the ubiquitination and degradation of TBX20. ![]() ![]() Here, we demonstrated that TBX20, a T-box TF family protein, was downregulated with hypermethylation of promoter in early-stage CRC tissues and correlated with a poor prognosis for CRC patients. Dysregulation of DNA methylation of TFs should be vital for the progression of CRC. ![]() ![]() Transcription factors (TFs) can determine cell fate and play fundamental roles in multistep process of tumorigenesis. DNA high methylation is one of driving force for colorectal carcinoma (CRC) pathogenesis. ![]()
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