Background and purpose
An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified.
Conclusion
Our findings provide the first evidence that miR-548b restrains HCC progression, at least partially, by downregulating HMGB1 and deactivating the PI3K-AKT pathway. Thus, miR-548b might be a novel target for the development of new therapies for HCC.
Methods
Expression levels of miR-548b in HCC tissues and cell lines were measured by reverse-transcription quantitative PCR. In vitro and in vivo functional assays were performed to determine the effects of miR-548b on the malignant phenotypes of HCC cells. In addition, the molecular mechanisms by which miR-548b regulates the initiation and progression of HCC were investigated in detail.
Purpose
An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified.
Results
miR-548b expression was weak in HCC tissues and cell lines. The low miR-548b expression significantly correlated with tumor size, TNM stage, and venous infiltration of HCC. In addition, exogenous miR-548b expression suppressed HCC cell proliferation, colony formation, and metastasis and induced apoptosis in vitro. Silencing of miR-548b exerted an opposite effect on these characteristics of HCC cells. Furthermore, miR-548b overexpression hindered tumor growth in vivo. Mechanistic analysis identified high-mobility group box 1 (HMGB1) as a direct target gene of miR-548b in HCC cells. Moreover, an HMGB1 knockdown reproduced the effects of miR-548b upregulation on HCC cells. Recovered HMGB1 expression reversed the effects of miR-548b on HCC cells. Notably, miR-548b overexpression deactivated the PI3K-AKT pathway in HCC cells in vitro and in vivo.