TRUB1 is a novel biomarker for promoting malignancy in colorectal cancer via NFκB signaling.

Abstract

Background: Colorectal cancer (CRC) is one of the most aggressive malignancies of the digestive tract, characterized by aberrant post-transcriptional RNA modifications, including pseudouridine (Ψ). TruB pseudouridine synthase family member 1 (TRUB1) is a key pseudouridine synthase but its role in CRC progression remains unclear.

Methods: Public databases and CRC cell lines were analysed to assess TRUB1 expression in CRC. Receiver-operating characteristic (ROC) curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic significance of TRUB1. The impact of TRUB1 on tumor proliferation and Ψ modification was examined in TRUB1-knock-down HCT116 cell lines. Mechanistically, RNA sequencing of control and TRUB1-knock-down HCT116 cells was conducted to identify potential pathways, which were validated by using real-time polymerase chain reaction (PCR), Western blot, and immunofluorescence assays.

Results: TRUB1 was significantly upregulated in CRC tumor tissues and cell lines. ROC analysis showed that TRUB1 had strong diagnostic potential and its overexpression was associated with poorer overall survival in CRC patients. In TRUB1-knock-down HCT116 cells, apoptosis increased and tumor growth slowed in nude mice, with a corresponding increase in apoptosis-related proteins and decreased Ψ modification. Mechanistically, RNA sequencing indicated that tumor necrosis factor α signaling via the nuclear factor kappa B (NFκB) pathway was activated in TRUB1-knock-down HCT116 cells. Further analysis identified Baculoviral inhibitor of apoptosis proteins repeat-containing 3 (BIRC3) as a potential downstream target gene that was regulated by TRUB1 in the NFκB pathway.

Conclusions: TRUB1 serves as a potential biomarker for CRC diagnosis and prognosis, and it can inhibit apoptosis in CRC cells via BIRC3-mediated NFκB signaling.