MiR-7-5p suppresses TGF-β-induced glycolysis and proliferation in intrahepatic cholangiocarcinoma by targeting MyD88.

Intrahepatic cholangiocarcinoma (ICC) is an insidious and aggressive malignancy with poor prognosis. Our previous research has suggested that miR-7-5p modulates the ICC cell phenotype by targeting MyD88; however, its downstream molecular mechanisms remain poorly elucidated. Considering that TGF-β signaling and aerobic glycolysis provide a favorable growth environment for tumors, this study aims to explored the relationship between the miR-7-5p/MyD88 axis and these metabolic characteristics. Bioinformatics methods were used to analyze the MyD88 expression in the GSE107943, and inferred its association with TGF-β signaling activity and glycolysis scores. Next, a series of experiments was conducted to evaluate the biological functions of MyD88 and miR-7-5p, with a TGF-β activator applied to elucidate potential mechanisms. A subcutaneous xenograft mouse model was used for in vivo validation. MyD88 expression was highly expressed in ICC samples, and its levels were positively correlated with TGF-β signaling activity and glycolysis scores. MyD88 knockdown attenuated the viability, migration, and glycolysis of ICC cells, thereby inhibiting tumor growth in vivo. Furthermore, MyD88 acted in a TGF-β-dependent manner, and TGF-β activation reversed the effects of MyD88 knockdown on malignant phenotype. Experiments also showed that MyD88 downregulation was caused by miR-7-5p, and then MyD88 overexpression reversed the suppressive effect of miR-7-5p on glycolysis. Collectively, miR-7-5p specifically targets MyD88, weakening glycolysis in ICCs by reducing TGF-β signaling activity, thus exerting an inhibitory effect on ICC.