Hepatitis B Virus-Related Hepatocellular Carcinoma is Induced by MicroRNA-181a Posted by: Maureen Newman February 17, 2014 Researchers at Chongqing Medical University in China broke new ground on an association between microRNAs and hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. The link between the two is formed by chronic hepatitis B virus (HBV), the most prominent cause (accounting for 55% of cases) for HCC. The researchers wanted to better understand the molecular mechanisms of HBV-related HCC, and they knew from previous work that miRNA-181a is up-regulated in HBV-expressing hepatocarcinoma cells, so they investigated miRNA expression in HCC cells. The results were published today in BioMed Central Cancer.
Lead author Chengcheng Zou and colleagues first transfected HBV-negative HCC cells to stably express HBV, then compared the amount of miRNA-181a production among HCC-HBV+, HCC-HBV-, and constitutively-HBV+ cells. As expected, the level of miRNA-181a expression was higher in both HBV+ cells than in HBV-cells. To investigate the implications of increased miRNA-181a, the scientists measured cell proliferation and identified that miRNA-181a-high cell number was approximately 1.3-times as large as miRNA-181a-low cell number. It was then identified that miRNA targets and inhibits E2F5, a transcription factor that negatively regulates the cell cycle, allowing the cells to leave G0 and begin proliferating. Cell proliferation and cancer go hand-in-hand, and it was next identified that miRNA-181a+ cells created larger tumors than miRNA-181a- cells when injected into mice.
These findings provide further evidence that HBV plays a role in promoting cell growth, and it may be due to miRNA-181a expression that drives cells into the cell cycle. Although more research is necessary to fully understand the relationship among miRNA-181a, HBV, and HCC, this work may drive a new therapy for stopping the progression of HCC through suppressing miRNA-181a .
This work was supported by The Major National S&T program (2013ZX10002002, ALH), Major project of Chongqing Science & Technology Commission (cstc2013jcyjC10002, ALH), and Natural Science Foundation Project of CQ CSTC (2010BB5359).
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