PLG inhibits Hippo signaling pathway through SRC in the hepatitis B virus-induced hepatocellular-carcinoma progression

• Published in: American journal of translational research 2021-01, Vol.13 (2), p.515-531
• Main Authors: Hu, Zhi-Gao, Chen, Yu-Bing, Huang, Mei, Tu, Jiang-Bo, Tu, Shu-Ju, Pan, Yu-Juan, Chen, Xue-Li, He, Song-Qing
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1943-8141; 1943-8141

Hepatitis B virus (HBV) infection is one main cause of hepatocellular carcinoma (HCC), but the mechanisms of pathogenesis still remain unclear. We screened the 1351 differentially expressed genes related to HBV-induced HCC by bioinformatics analysis from databases and found that Plasminogen (PLG) may be a key gene in HBV-induced HCC progression. Then, we used a series of experiments and to explore the roles of PLG in HBV-HCC progression, such as qRT-PCR, western blot, ELISA, flow cytometry and TUNEL assay, subcutaneous xenografts and histopathological analysis to reveal the underlying mechanisms. PLG was over-expressed in HBV positive hepatocellular carcinoma tissues and cells. PLG silencing promoted HBV-HCC cell apoptosis and suppressed the growth of HBV-induced HCC xenografts both through inhibiting HBV replication. Then, GO and KEGG analysis of these differentially expressed genes revealed that the Hippo pathway was the key pathway involved in HBV-induced HCC, and SRC, a downstream target gene of PLG, was highly expressed in HBV-induced HCC and related to the Hippo pathway. Thus, we speculated that PLG promoted HBV-induced HCC progression through up-regulating and activating the expression of SRC and promoting Hippo signaling pathway function on HBV-HCC cell survival. Our study suggests PLG may be an activator of HBV-infected hepatocellular carcinoma development, as a novel prognostic biomarker and therapeutic target for HBV-HCC.