Knocking Down in Colorectal Cancer: Implications for Apoptosis and Cell Cycle Arrest via the p53 Signaling Pathway.

Background: Preventing the progression and recurrence of colorectal cancer (CRC) remains a clinical challenge due to its heterogeneity and drug resistance. This underscores the need to discover new targets and elucidate their cancer-promoting mechanisms. This study analyzed the cancer-promoting mechanisms of tryptophanyl-tRNA synthetase 1 () in CRC.

Methods: Clinical data and RNA expression profiles of CRC patients in public databases were analyzed using bioinformatics to determine the expression of . A knockdown assay was conducted with HCT116 and RKO cell lines to systematically assess the effects of on CRC cell proliferation, migration, cell cycle, and apoptosis. These assessments employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, wound healing and transwell assays, flow cytometry, and xenograft tumor assays. Additionally, RNA sequencing and gene enrichment-based analysis were performed following knockdown to detect gene expression changes and related pathways.

Results: was overexpressed in CRC tissues ( < 0.05). Downregulation of inhibited the growth and migration of RKO and HCT116 cell lines ( < 0.05). This inhibitory effect on tumor growth was also observed in xenografts in nude mice after knockdown ( < 0.01). Flow cytometry revealed an increase in apoptosis and cell cycle arrest following knockdown ( < 0.05). Transcriptome sequencing analysis showed that reduced expression of activated the p53 signaling pathway and apoptosis while suppressing DNA replication and the cell cycle. The p53 transcriptional inhibitor pifithrin-α partially prevented the activation of caspase 3 and reduced the levels of c-poly-ADP-ribose polymerases 1 () and cyclin-dependent kinase inhibitor 1A ().

Conclusion: was highly expressed in CRC, and its low expression was identified as a risk factor for CRC progression and recurrence. The current findings provide a theoretical basis for the development of therapeutic agents targeting and elucidate its mechanism in CRC progression.