Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is among the most common malignant tumors
In order to study the mechanism of SOR-resistance, we developed HepG2/SOR cells
In order to identify the molecular mechanism of miR-92b, we investigated expression of key proteins in the PI3K/AKT/mTOR signaling pathways
Summary
Hepatocellular carcinoma (HCC) is among the most common malignant tumors. It accounts for approximately 90% of all liver cancers, and remains the major cause of cancer-related death across the world [1,2]. The overall survival rate of HCC patients remains low not merely due to the recurrence and metastasis of HCC itself, and due to a lack of sensitive detection methods and effective treatments [3,4]. Sorafenib (SOR) is the preferred multi-target kinase inhibitor for treatment of advanced HCC, and can improve overall survival rate of advanced HCC patients [6,7]. The molecular mechanisms of SOR resistance in HCC remains unknown
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