MicroRNA 133A Regulates Squalene Epoxidase Expression in Colorectal Cancer Cells to Control Cell Proliferation and Cholesterol Production

Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of MIR133A. Using the MIR133A KI cell lines, which knocked-in MIR133A1 or MIR133A2 in CRC cell lines, and CRC cells transfected with siSQLE, we found that MIR133A regulated the proliferation and migration of CRC cells by modulating SQLE-mediated PIK3CA-AKT1 and CYP24A1 signaling. We also found that cholesterol production was regulated by MIR133A in CRC cells. Conclusions: Our results suggest that MIR133A is an important therapeutic target for colorectal cancer.