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Exosomal miR-1821, miR-301a, and miR-373 as potential biomarker in NASH-induced liver cirrhosis with hepatocellular carcinoma.

Allia Najmie Muhammadi Yusuf, MD Raja Affendia Raja Ali, Khairul Najmia Muhammad Nawawi, Norfilza Mohd Mokhtar

Exosomal miRNAs was reported to play roles in the pathogenesis of various types of malignancies. This study aimed to identify the expression level of chosen miRNAs (miR-182, miR-301a and miR-373) in exosomes of serum and ascitic fluid in patients with non-alcoholic steatohepatitis (NASH)-related liver cirrhosis with or without hepatocellular carcinoma (HCC). A literature search was performed to identify potential miRNAs involved in this cancer. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH-related liver cirrhosis with or without HCC. Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR-373 were determined using qPCR. Serumderived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold-change of 1.77, 2.52, and 1.67 (p<0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. The expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold-change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p<0.05). High expression of the selected exosomal miRNAs in both serum and ascitic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with HCC.