This favorable role may in part explain association of miR-34a with SVR. In addition, miR-34a may target and downregulate hepatocytes nuclear factor-4��, which was shown to induce multidrug resistance proteins. The observed significant negative correlation between miR-34a and viral load may also explain its association with SVR; where SVR were demonstrated to have lower HCV RNA than NR group. This correlation, despite weak, may also in part indicate a mutual Diprenorphine relationship between HCV and miR-34a. miR-34a expression was increased, or decreased in different HCV models. However, whether it is being directly altered or altering the virus yet to be studied. We observed that miR-34a was Bay 36-7620 negatively correlated with AST levels. In contrast, a previous study reported a positive correlation. The present study demonstrated significant upregulation of miR-296 in CHC. miR-296 was increased in PBMCs, or decreased in liver biopsy from CHC patients. Controversial results between miRNAs in serum and liver tissue have been observed in drug-induced liver injury. However, there are several reports of miRNAs that are upregulated in the serum as well as infected or cancerous tissue. Meanwhile, miR-296 was induced by IFN-�� treatment and inhibited HCV replication in human hepatoma cell line by directly targeting the viral RNA. miR-296 was also induced by INF-�� treatment in human PBMCs of healthy individuals as well as CHC patients. Thereby, miR-296 may be a potential strategy to protect against liver injury during CHC. It is unknown whether HCV has evolved a counter mechanism to this antiviral miRNA, although some studies suggest that such a mechanism might exist. Significant upregulation of serum miR-130a in CHC was observed. Similarly, miR-130a was upregulated in HCV Con-1 replicon, HCV-infected hepatocytes, and in liver biopsy from CHC patients, thus, these could be reflected in the serum. In contrast, miR-130a was downregulated upon acute HCV infection to Huh7.5 cells, or unchanged in HCVexpressing Huh7 cells. The discrepancies in miRNA expression profiles between different studies may be due to different in vitro models and cell types, or different HCV genotypes. miR-130a was induced by INF-�� treatment in Huh cells and in HCV-infected hepatocytes and was shown to potentially regulate HCV. miR-130a/301 may interfere with the INF pathway by targeting interferon regulatory factor-1 and STAT3 genes in HCV-infected cells. miR-130a was predicted to target endocytosis and transforming growth factor-�� signaling, that affect cell growth and apoptosis. miR-130a was upregulated by HCV and facilitated HCV replication by targeting antiviral interferon inducible trans-membrane protein ; knockdown of miR-130a upregulated IFITM expression and inhibited HCV replication in hepatocytes. Similarly, miR-130a augmented HCV replication in infected cells as anti-miR-130a downregulated HCV replication. Conversely, miR-130a downregulated HCV replication by restoring the innate immune response.