MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4

Rui-Peng Zheng, 1 Dong-Kai Ma, 2 Zhuo Li, 3 Hai-Feng Zhang 1 1Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changchun, Jilin Province 130012, People’s Republic of China; 3Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Hai-Feng ZhangDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 13756696677Email HaifengZhang159@outlook.comBackground: 5-fluorouracil (5-FU) is a common drug for hepatic carcinoma (HCC), but the drug resistance of clinical chemotherapy restricts its use. Studies have demonstrated that miRNA molecules can act as a chemoresistance regulator in drug resistance of tumors, whereas the role of miR-145 in the 5-FU-resistant HCC remains unclear.Objective: To explore the prognostic value of miR-145 in HCC and its molecular mechanism in 5-FU-resistant HCC cells.Methods: A qRT-PCR assay was conducted to quantify miR-145 in HCC tissues and 5-FU-resistant HCC cells. The Cell Counting Kit-8 (CCK-8) and flow cytometry were adopted to analyze the proliferation and apoptosis of 5-FU-resistant HCC cells. The Western blot was adopted to quantify toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and apoptosis-related proteins. Moreover, an in vivo tumor xenotransplantation of nude mice was conducted to determine the effect of miR-145 on 5-FU-resistant HCC cells.Results: MiR-145 was expressed lowly in HCC tissues and cells, and linked to high TNM staging and lymph node metastasis of HCC patients. Down-regulation of miR-145 indicated a poorer prognosis and it promoted drug resistance of HCC cells and inhibited cell apoptosis. In contrast, miR-145 overexpression improved the sensitivity of HCC cells to 5-FU and ...