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Effect of Differentially Expressed MicroRNAs 602 and 323-5p on Hepatitis C Virus Genotype 1b Viral Load in Infected Liver Cells

Samina Noorali, Muhammad Sheraz, Shaniqua S Tisdale, Stacey S Dallas, Lauren M Simons, Raquel S White and Verlie A Tisdale

Background: Hepatitis C virus (HCV) infection is a major cause of severe liver disease worldwide. Interferon/ ribavirin treatment remains the standard therapeutic regimen for HCV infection. Emerging evidence suggests that microRNAs, a class of small non-coding RNAs, are involved in controlling viral infection. Liver-specific microRNA, miR-122 has been widely studied, which facilitates HCV replication, and anti-miR-122 is used as a mono-therapy in patient with HCV infection. Studies show that anti-miR-122 might have some negative impacts on the hepatocytes’ metabolism which could be prone to emergence of resistance. Hence, other microRNAs should be investigated, which could be potential candidates for treatment of HCV infection.

Methods: We performed microarray profile of 704 human microRNAs in Huh-7.5 cells (hepatocytes) transfected with HCV genotype 1b RNA. Microarray profile demonstrated that miR-602 was up-regulated 1256.32 fold, and miR- 323-5p was down-regulated -2182.03 fold. We further investigated the intracellular expression of miR-602 and miR- 323-5p in Huh-7.5 cells not transfected with HCV genotype 1b RNA. We studied the sequestering effect of miR-602 and miR-323-5p on HCV genotype 1b RNA accumulation in Huh-7.5 cells using their respective microRNA inhibitors, and their anti-HCV activity using qRT-PCR.

Results: Here, we show that miR-602 and miR-323-5p are normally expressed in Huh-7.5 cells. HCV genotype 1b RNA accumulation increased and decreased in transfected Huh-7.5 cells with inhibitors directed against miR-602 and miR-323-5p, respectively. Our results also demonstrated that when miR-602 was transfected with HCV genotype 1b RNA, it inhibited HCV genotype 1b accumulation in Huh-7.5 cells.

Conclusions: Our results suggest that miR-602 and miR-323-5p which were differentially expressed in microarray profiling, can be used as a potential early detection markers for HCV genotype 1b infection and miR-602 can be a candidate therapeutic biomarker for HCV treatment.