The circMTCL1/miR-145-5p/BMP3 axis suppresses colorectal cancer cell growth by mediating the MAPK signaling pathway.

Abstract

Circular RNAs play key roles in colorectal cancer (CRC). Here, we examine the function and underlying mechanism of circMTCL1 in CRC. The expression of circMTCL1 in CRC tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). The function of circMTCL1 was elucidated through overexpression and knockdown studies. Furthermore, a combination of Fluorescence in situ hybridization (FISH), nuclear-cytoplasmic fractionation, RNA immunoprecipitation (RIP), qRT-PCR, Western blotting, and dual-luciferase reporter assays was employed to elucidate the tumor-suppressive mechanism of circMTCL1 in CRC. circMTCL1 was significantly downregulated in CRC tissues compared to adjacent normal tissues, showing a 17.08-fold decrease (P < 0.001). It functioned as a competing endogenous RNA (ceRNA) by specifically binding to miR-145-5p, thereby modulating the expression of Bone Morphogenetic Protein 3 (BMP3). Overexpression of circMTCL1 markedly inhibited the proliferation, migration, and invasion of CRC cells, resulting in a 3.76-fold decrease in proliferation (P < 0.001), and 1.58-fold and 2.00-fold decreases in migration and invasion, respectively (P < 0.001). Furthermore, circMTCL1 overexpression upregulated BMP3 expression by 1.60-fold (P < 0.001). Further investigation revealed that circMTCL1 regulates tumor progression by suppressing the activation of the MAPK signaling pathway. circMTCL1 acts as a tumor suppressor in CRC. Its mechanism likely involves sponging miR-145-5p to regulate BMP3 expression and modulating the MAPK signaling pathway. These findings provide a new perspective on the pathogenesis of CRC and identify a potential therapeutic target for clinical intervention.