Identification of microRNA‐96‐5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma. Issue 1 (14th June 2021)

• Record Type: Journal Article
• Authors: Matsui, Takeshi; Hamada‐Tsutsumi, Susumu; Naito, Yutaka; Nojima, Masanori; Iio, Etsuko; Tamori, Akihiro; Kubo, Shoji; Ide, Tatsuya; Kondo, Yasuteru; Eguchi, Yuichiro; Komori, Atsumasa; Morine, Yuji; Shimada, Mitsuo; Utsunomiya, Tohru; Shirabe, Ken; Kimura, Koichi; Hiasa, Yoichi; Chuaypen, Natthaya; Tangkijvanich, Pisit; Naiki‐Ito, Aya; Takahashi, Satoru; Ochiya, Takahiro; Tanaka, Yasuhito
• Is Part Of: Hepatology research. Volume 52:Issue 1(2022)
• Page Start: 93
• Page End: 104
• Publication Date: 2021-06-14
• Subjects: HCC recurrence -- hepatocellular carcinoma (HCC) -- microRNA -- miR‐96‐5p; Liver -- Diseases -- Periodicals; Liver Diseases -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1111/hepr.13674
• Languages: English
• ISSNs: 1386-6346

Abstract

Abstract: Aim: The microRNA (miR) clusters miR‐183/96/182 and miR‐217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC‐HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC‐HCC and analyze the antitumor effects of miR‐96‐5p. Methods: The association between recurrence‐free survival of 111 NBNC‐HCC patients and the levels of miR‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, miR‐216a‐5p, and miR‐216b‐5p in tumor and adjacent tissues was investigated. The impact of miR‐96‐5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. Results: MicroRNA‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, and miR‐216b‐5p were significantly upregulated in tumor tissues compared to the adjacent tissues ( p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR‐182‐5p ( p = 0.007) and miR‐217‐5p ( p = 0.008) were associated with poor recurrence‐free survival. In contrast, a low tumor/adjacent ratio of miR‐96‐5p ( p < 0.001) was associated with poor recurrence‐free survival. It suggested that further upregulation of miR‐96‐5p in tumors might have an inhibitory effect on recurrence. Transfection of miR‐96‐5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA‐96‐5p also suppressed proliferation and invasion, which inhibited epithelial‐to‐mesenchymal transition of HCC cells. Conclusion: MicroRNA‐96‐5p as a tumor suppressor would be valuable to stratify NBNC‐HCC patients at high risk of recurrence.