This study investigates the feasibility of circMFSD12 as a potential therapeutic target by analyzing its expression in colorectal cancer and its impact on tumor cell proliferation, migration, invasion, and sensitivity to 5-fluorouracil (5-FU), aiming to provide new insights for the treatment of colorectal cancer.

Human RNA datasets (GSE172229, GSE166973, GSE147597) from colorectal cancer tissues, normal colonic tissues, and normal intestinal tissues were retrieved from public databases to screen for downregulated circRNAs in colorectal cancer. The expression level of circMFSD12 in colorectal cancer cell lines was analyzed using quantitative real-time PCR (qRT-PCR). Overexpression plasmids of circMFSD12 were constructed and transfected into colorectal cancer cell lines LoVo and SW620 to evaluate their effects on cell proliferation, migration, and invasion through EdU staining, wound healing assays, and Transwell assays. Additionally, the effects on 5-FU sensitivity were assessed using CCK8 assays and flow cytometry experiments, and the potential molecular mechanisms were further investigated through bioinformatics analysis and miRNA pull-down experiments.

Data analysis indicated that circMFSD12 is downregulated in colorectal cancer tissues (selection criteria: logFC<-0.5) and cells (expression in normal colonic epithelial cells NCM460: 1.00±0.14, and in colorectal cancer cells: HCT116: 0.72±0.08, LoVo: 0.42±0.10, SW480: 0.72±0.04, SW620: 0.48±0.07) (P<0.05). In vitro experiments showed that overexpression of circMFSD12 significantly inhibited colorectal cancer cell proliferation (LoVo: 52%±5.3% vs. 22%±3.7%, P<0.001; SW620: 56%±10% vs. 26%±4.0%, P<0.001), migration (LoVo: 75%±5.5% vs. 34%±5.7%, P<0.001; SW620: 54%±7.5% vs.22%±5.6%, P<0.001), and invasion (LoVo: 104±18.6 vs. 41.7±10.2, P<0.01; SW620: 86.7±16.5 vs. 34.7±4.9, P<0.01), and enhanced cellular sensitivity to 5-FU (LoVo: Control: 2.5±0.7 vs.7.4±1.0, P<0.01, 5-FU: 11.8±1.9 vs. 28.6±1.9, P<0.001; SW620: Control: 2.2±0.4 vs. 8.1±1.3, P<0.01, 5-FU: 10.2±1.4 vs. 23.4±2.3, P<0.001). Bioinformatics analysis and experimental validation suggest that circMFSD12 suppresses colorectal cancer cell behaviors by regulating the expression of miR-887-3p and PPP1R12B.

circMFSD12 regulates miR-887-3p/PPP1R12B, significantly affecting the biological behavior of colorectal cancer cells, indicating that it has good prospects as a novel molecular biomarker and potential therapeutic target.