Reciprocal Control Of MiR-197and IL-6/STAT3Pathway In Hepatocellular Carcinoma

Signal transducer and activator of transcription3(STAT3) is one of the key players in liver cancer. Increased levels of phosphorylated STAT3(p-STAT3) have been detected in many cancers including hepatocellular carcinoma (HCC), and are usually associated with a more aggressive phenotype and poor prognosis. In addition to aberrant activation of STAT3, upregulation of total STAT3was also detected in HCC, for which the underlying mechanisms and significance remain to be fully elucidated. Here we report that a reciprocal regulation exists between miR-197and the IL-6/STAT3inflammatory signaling pathway in HCC. We found that IL-6stimulation increased total STAT3expression at protein level but not mRNA level in HCC cells, suggesting the existence of post-transcriptional regulation of STAT3. Our study showed that IL-6/STAT3pathway decreases expression of miR-197in HCC, which amplifies IL-6/STAT3pathway and contributes to HCC progression. miR-197can significantly inhibit HCC growth both in vitro and in vivo. In addition, IL-6/STAT3-induced downregulation of miR-197in HCC may be via affecting Drosha binding to primary miR-197(pri-miR-197) and thus reducing mature miR-197generation. Our study suggests that miR-197may serve as a potential therapeutic target for interfering the IL-6/STAT3inflammatory pathway in HCC.