MicroRNA-92b augments sorafenib resistance in hepatocellular carcinoma via targeting PTEN to activate PI3K/AKT/mTOR signaling

• Published in: Brazilian journal of medical and biological research 2021-01, Vol.54 (9), p.e10390-e10390
• Main Authors: Cheng, Zhouyang, Ni, Qingfeng, Qin, Lei, Shi, Yang
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; BIOLOGY; Cancer; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Care and treatment; Cell Line, Tumor; Cell Proliferation; Comparative analysis; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; Hepatoma; Humans; Immunofluorescence; Infection; Inhibitor drugs; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; MEDICINE, RESEARCH & EXPERIMENTAL; MicroRNA; MicroRNA-92b; MicroRNAs; MicroRNAs - genetics; miRNA; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; PTEN; PTEN Phosphohydrolase - genetics; PTEN protein; Resistance; Signal Transduction; Sorafenib; Sorafenib - pharmacology; Targeted cancer therapy; TOR protein; TOR Serine-Threonine Kinases; Transfection; Tumor cells; Western blotting
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431X2020e10390

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.