FOXQ1 Suppressing Apoptosis in Colorectal Cancer Cells by P53 Deacetylation.

Objective: To investigate the impact of Forkhead box Q1 (FOXQ1) expression on platinum-based chemoresistance in colorectal cancer (CRC) cells, and to examine the regulatory function of FOXQ1 on Sirtuin 1 (SIRT1) protein expression and P53 protein deacetylation levels during the DNA damage response (DDR).

Study design: An experimental study. Place and Duration of the Study: Second Department of Gastrointestinal Surgery, General Surgery Centre, Qingdao Municipal Hospital, Affiliated to Qingdao Medical College, Qingdao University, Qingdao, China, from October 2023 to December 2024.

Methodology: Gene expression levels of FOXQ1 in CRC cells and SW620 cells treated with cisplatin (CDDP) were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The t-test was used to compare the gene expression levels between the two groups. Three gene-edited SW620 cell models were established: FOXQ1 overexpression (oe-FOXQ1), FOXQ1 RNA interference (sh- FOXQ1), and a negative control (NC). CCK-8 assays measured CDDP's half-inhibitory concentration (IC50), while flow cytometry, calcein-AM/PI staining, and colony formation evaluated cell apoptosis and survival. Western blot analysed SIRT1 and acetylated p53, and the SIRT1 inhibitor (S)-Selisistat explored FOXQ1-related pathways.

Results: FOXQ1 was highly expressed in CRC. CDDP treatment further increased its expression in SW620 cells. FOXQ1 overexpression enhanced CDDP resistance, elevated SIRT1 levels, and promoted P53 deacetylation. (S)-Selisistat reversed P53 deacetylation and reduced CDDP resistance in oe-FOXQ1 cells.

Conclusion: FOXQ1 promotes chemoresistance in CRC by upregulating SIRT1 expression and promoting P53 deacetylation, thereby inhibiting apoptosis triggered by DDR.

Key words: Colorectal cancer, Forkhead Box Q1, Sirtuin 1, P53 Acetylation, Apoptosis.