Functional characterization of ALMS1-IT1 in colorectal cancer following TRPM4-correlated lncRNA screening

Background The long non-coding RNA (lncRNA) ALMS1-IT1 has been implicated in colorectal cancer (CRC), but its relationship with cPLA2/PTGS2 expression remains unclear. Methods Transcriptomic and clinical data from 620 patients in TCGA-COAD and TCGA-READ were analyzed; somatic mutation analyses included patients with available mutation data. TRPM4-correlated lncRNAs were screened, and an exploratory prognostic score was developed using Cox and LASSO regression and evaluated using an internal training–validation split. Pathway, immune, mutational, and predicted drug-response features associated with the score were examined. The effects of ALMS1-IT1 knockdown were assessed in CRC cells, and a subcutaneous xenograft assay was performed using siRNA-transfected SW480 cells. Results The five-lncRNA score comprised AC074212.1, ALMS1-IT1, RBM26-AS1, AC009133.1, and AC147067.1. Patients in the high-risk group had poorer overall survival in both the training and internal validation cohorts. The time-dependent area under the receiver operating characteristic curve (AU-ROC) was 0.689, 0.667, and 0.623 at 1, 3, and 5 years, respectively. ALMS1-IT1 expression was higher in SW480 and RKO cells than in NCM460 cells. Knockdown reduced EdU incorporation and colony formation, delayed wound closure, and decreased Transwell migration and invasion. These changes were accompanied by reduced PLA2G4A and PTGS2 transcript levels and lower cPLA2 and PTGS2 protein abundance. At the 2-week endpoint, xenograft tumors in the si-ALMS1-IT1 group weighed less than control tumors. Conclusion TRPM4-correlated screening identified a five-lncRNA score associated with CRC survival and supported functional investigation of ALMS1-IT1. The findings support further investigation of ALMS1-IT1-associated phenotypes and cPLA2/PTGS2 expression changes in CRC. The prognostic score requires external validation, and the mechanisms underlying these observations remain to be determined.