Ubiquitin-conjugating enzyme E2T(UBE2T) promotes colorectal cancer progression by facilitating ubiquitination and degradation of p53.

Objectives: The expression level of Ubiquitin-conjugating enzyme E2T (UBE2T) is upregulated in various types of human tumors. We explored the correlation and regulatory mechanism of UBE2T in the development of colorectal cancer (CRC).

Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine the expression of UBE2T in the CRC tissues and cell lines. Immunohistochemical staining, spearman correlation analysis, and Kaplan Meier-survival analysis were used to demonstrate the correlation between UBE2T high expression level and the clinical characteristics of malignant patients and the overall survival. The proliferation, apoptosis, migration and invasion of CRC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, transwell, and flow cytometry. Furthermore, the expression of cell proliferation and apoptosis related proteins and ubiquitination of p53 were detected by western blot.

Results: UBE2T was up-regulated in CRC tissues and cell lines, and high expression level of UBE2T was correlated with the clinical characteristics of malignant of CRC patients (P<0.05), and patients with high expression level of UBE2T had lower overall survival (P=0.0455). In addition, UBE2T could promote the growth, proliferation, invasion and metastasis of CRC cells and inhibit the apoptosis. At the same time, knockdown of UBE2T inhibited the growth of transplanted tumor in mice of subcutaneous CRC model. Moreover, our experimental results proved that UBE2T regulated the expression of downstream related proteins through ubiquitination of p53 protein to promote the occurrence and development of CRC.

Conclusion: Our study elucidated that high expression of UBE2T would enhance the development of CRC, and then further explored its molecular mechanism both in vitro and in vivo. The results indicated that UBE2T facilitated ubiquitination and degradation of p53, which predicts the possibility of UBE2T as one of molecular diagnosis markers, prognostic indicators and therapeutic drug targets of CRC patients.