MicroRNA-941 Acts as a Novel Prognostic Predictor and Oncogenic Driver in Colorectal Cancer.

Abstract

Aim: This study aims to ascertain the expression status, clinical significance, and biological function of microRNA-941 (miR-941) in colorectal cancer (CRC). It elucidates the role of miR-941 in tumor development and the underlying mechanism involving the transcriptional repressor GATA binding 1 (TRPS1).

Methods: Serum samples were collected from 150 CRC patients and 150 healthy controls to examine the relative amounts of miR-941. The diagnostic value of miR-941 was evaluated by plotting receiver operating characteristic (ROC) curves. Kaplan-Meier and Cox regression analyses were employed to assess the prognostic implications of miR-941. Functional experiments were conducted in CRC cell lines. The target gene of miR-941 was identified and confirmed through bioinformatics analysis and a dual-luciferase reporter assay.

Results: An increased level of miR-941 was found in CRC patients and cell lines (p < 0.001). The preliminary diagnostic performance showed an area under the ROC curve (AUC) of 0.882. Its high expression was tightly in relation to advanced tumor node metastasis stage, lymph node metastasis, and inferior overall survival, serving as an independent prognostic factor (HR = 2.217, p = 0.005). Functionally, inhibition of miR-941 suppressed cellular behaviors and induced changes with ferroptosis phenotypes. Mechanistically, TRPS1 was predicted and verified to be a direct target of miR-941 at both mRNA and protein levels. Moreover, knockdown of TRPS1 could reverse the tumor-suppressive effects and ferroptosis-related changes caused by miR-941 inhibition.

Conclusion: Our results identify miR-941 as a novel oncogenic driver in CRC through targeting of TRPS1, serving as a valuable prognostic indicator.