Abstract 3429: Oncogenic function of miR-23b-3p in hepatocellular carcinoma

Background: miR-23b has been identified as various cancer-related biomarkers. Interestingly, it works as an oncogenic miRNA in lymphoma, renal cancer and glioma, while it works as a tumor suppressor miRNA in pancreatic cancer, bladder cancer and prostate cancer (Donadeli M et al, Cancer Lett, 2014). We have previously reported miR-23b-3p as a oncomiR in NSCLCs (Begum S, Hayashi M et al, Sci Rep, 2015). To find the correlation to other carcinogenesis, we focused on miR-23b function in hepatocellular carcinoma (HCC). Methods: miR-23b-3p expression was examined in 9 HCC cell lines (SK-Hep1, HuH2, HLE, PLC/PRF/5, HuH1, HuH7, HLF, Hep3B, HepG2). The downstream of miR-23b-3p overexpression was examined by Cancer Pathway Finder (Qiagen). Results were applied to 125 clinical HCC samples (2002-2011 surgically resected). Results: Transfection experiments were performed for HepG2 (miR-23b-3p highly expressed) by siRNA and for SK-Hep1 (lowly expressed) by miRNA mimic. Cancer cell proliferation was activated by miR-23b-3p overexpression, and diminished by its inhibition. In order to find the associated genes, miR-23b-3p overexpressed SK-Hep1 cells were compared with parental SK-Hep1 cells by global gene expression analysis. ANGP1, ERCC5 and G6PD genes were upregulated, while KDR, WEE1, OCLN genes were downregulated. We also detected additional two genes (AUH and MICU3) by TargetScan Release 5.2. Clinical HCC samples were divided into miR-23b-3p upregulated 48 cases (38%) and downregulated 77 cases (62%). Upregulated cases were correlated with aged patients (P=0.015), capsule invasion positive (P=0.039) and serosal invasion positive (P=0.049). Also, they showed significantly poor recurrence free survival (HR=1.64, P=0.037, 95%CI:1.03-2.59) and overall survival (HR=3.10, P=0.001, 95%:1.57-6.29) in multivariable analysis. Conclusion: miR-23b-3p increased the HCC cell proliferation, and indicated the invasive type of HCCs. It functions as a oncogenic biomarker in HCCs and might be a therapeutic target. Citation Format: Hiroshi Tanabe, Masamichi Hayashi, Hiroyuki Sugimoto, Keisuke Kurimoto, Sho Hirabayashi, Mitsuro Kanda, Hideki Takami, Yokiko Niwa, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Masahiko Koike, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera. Oncogenic function of miR-23b-3p in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC.