Search

Background and Aim. Aberrant activationof theTGF-𝛽1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs.Theaim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic ratmodel induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195.The expression levels of miR-195, Smad7, and 𝛼-SMAin HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamineinduced liver fibrotic rats (𝑃 < 0.05). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3󸀠UTR of Smad7 (𝑃 < 0.05).ThemiR-195 mimics activated HSCs, further elevated miR-195 and 𝛼-SMA (𝑃 < 0.01), and reduced the Smad7 level (𝑃 < 0.05). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and 𝛼-SMA (𝑃 < 0.01), and upregulated the expression of Smad7 (𝑃 < 0.05). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7. [ABSTRACT FROM AUTHOR]

As the fifth most common cancer in men and the eighth most common cancer in women, hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, with standard chemotherapy and radiation being minimally effective in prolonging survival. Virus hepatitis, particularly HBV and HCV infection is the most prominent risk factor for HCC development. Mammalian target of rapamycin (mTOR) pathway is activated in viral hepatitis and HCC. mTOR inhibitors have been tested successfully in clinical trials for their antineoplastic potency and well tolerability. Treatment with mTOR inhibitor alone or in combination with cytotoxic drugs or targeted therapy drug scan significantly reduces HCC growth and improves clinical outcome, indicating that mTOR inhibition is a promising strategy for the clinical management of HC. [ABSTRACT FROM AUTHOR]