PTBP3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining UBE4A mRNA stability.

The RNA binding protein PTBP3 was recently reported to play a critical role in multiple cancers, and the molecular mechanisms involved RNA splicing, 3' end processing and translation. However, the role of PTBP3 in colorectal cancer (CRC) remains poorly explored. Herein, PTBP3 was upregulated in CRC and associated with a poor prognosis. PTBP3 knockdown in colorectal cancer cell lines restricted CRC proliferative capacities in vitro and in vivo. Mechanistically, PTBP3 regulated the expression of the E3 ubiquitin ligase UBE4A by binding the 3' UTR of its mRNA, preventing its degradation. UBE4A participated in P53 degradation, and PTBP3 knockdown in colorectal cancer cell lines showed increased P53 expression. UBE4A overexpression rescued PTBP3 knockdown-induced inhibition of CRC cell proliferation and P53 expression. Our results demonstrated that PTBP3 plays an essential role in CRC cell proliferation by stabilizing UBE4A to regulate P53 expression and may serve as a new prognostic biomarker and effective therapeutic target for CRC.