MicroRNA-345-3p expression inhibits colorectal cancer liver metastasis by targeting KHDRBS1 and TGF-β signaling pathway

Abstract Objective The aim of this study was to investigate the association of microRNA-345-3p (miR-345-3p) with liver metastasis in colorectal cancer (CRC) and to explore its underlying molecular mechanisms using in vitro approaches. Methods Serum specimens were collected from 110 CRC patients and 90 healthy individuals. Quantitative real-time PCR (qRT-PCR) was employed to assess the expression levels of miR-345-3p and KH RNA binding domain containing, signal transduction associated 1 (KHDRBS1) expression. The associations of miR-345-3p with clinical pathological characteristics, survival, and liver metastasis were analyzed. In vitro cell experiments were conducted to validate the effects of miR-345-3p on CRC cell growth and epithelial-mesenchymal transition (EMT). Target genes and signaling pathways were verified using luciferase reporter assays, rescue experiments, and Western blot analysis. Results A significant decrease in miR-345-3p expression was observed in CRC patients with liver metastasis. Low levels of miR-345-3p were correlated with advanced tumor node metastasis (TNM) stages, deeper invasion, lymph node metastasis, and poorer prognosis. Overexpression of miR-345-3p inhibited CRC cell growth and suppressed EMT-associated molecular changes. Bioinformatics analyses and experimental results confirmed KHDRBS1 as a direct target gene of miR-345-3p. Furthermore, rescue experiments demonstrated that overexpression of KHDRBS1 reverses the tumor-suppressive effects of miR-345-3p, indicating that miR-345-3p functions by regulating the transforming growth factor-β (TGF-β) signaling pathway. Conclusions Decreased circulating levels of miR-345-3p are associated with liver metastasis in CRC. In vitro studies suggest that miR-345-3p may exert its tumor-suppressive effects by targeting KHDRBS1 and suppressing the TGF-β signaling pathway, thereby inhibiting CRC cell migration and invasive capacity.