The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

Liver cancer is the fifth most common cancer in the world, and the third leading cause of cancer death worldwide (1). Despite recent progress in disease diagnosis and treatment, the long-term prognosis of patients with liver cancer is still poor. For patients with advanced liver cancer, the overall 5-year survival rate is less than 5% (2). The main challenge of liver cancer treatment is recurrence and metastasis in the liver, which leads to a poor prognosis of liver cancer patients (3). MicroRNA is a class of non-coding RNA of 20 to 22 nucleotides, which can effectively regulate various biological processes, including cell proliferation, migration, differentiation, and apoptosis (4). The uncontrolled expression of microRNA is closely related to the pathogenesis of cancer, and it may act as a tumor suppressor gene or oncogene to promote the occurrence and development of liver cancer (5). Therefore, further research on the expression pattern and the role of microRNA may supply a new diagnostic and therapeutic target for liver cancer. miR-212 is a new miRNA associated with cancer, and it has been found that miR-212 is involved in the progress of different types of human cancers and down-regulated in liver cancer tissues (6). Besides, some studies have shown that the up-regulation of miR-212 inhibits the migration and tumorigenicity of human hepatocellular carcinoma (7). miR-212 is a potential prognostic biomarker of hepatocellular carcinoma, overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo (8). Hepatitis B virus triggers apolipoprotein B mRNA editing enzyme catalytic subunit 2 (APOBEC2) expression through miR 122 regulation and affects the proliferation of liver cancer cells (9). miR-212 inhibits the growth of human liver cancer tumors by targeting FOXA1 (10). A study has exhibited that aberrant hypermethylation-induced downregulation of miR-212-3p results in overexpression of Mucin 13 in intrahepatic cholangiocarcinoma, leading to metastasis via activation of the EGFR/PI3K/AKT signaling pathway (11)