MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma

Weiyou Zhu; Jing Qian; Ling Ma; Pei Ma; Fengming Yang; Yongqian Shu

doi:10.18632/oncotarget.18060

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Research Papers:

MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma

Weiyou Zhu, Jing Qian, Ling Ma, Pei Ma, Fengming Yang and Yongqian Shu _

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Oncotarget. 2017; 8:65218-65229. https://doi.org/10.18632/oncotarget.18060

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Abstract

Weiyou Zhu1,2, Jing Qian1, Ling Ma1, Pei Ma1, Fengming Yang1 and Yongqian Shu1

1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China

2Oncology Center, Shengze Hospital of Nanjing Medical University, Wujiang, Jiangsu Province, P.R. China

Correspondence to:

Yongqian Shu, email: [email protected]

Keywords: miRNA, proliferation, untranslated regions, hepatocellular carcinoma, SMYD3

Received: March 20, 2017 Accepted: April 15, 2017 Published: May 22, 2017

ABSTRACT

BACKGROUND & AIMS: The miRNAs are demonstrated to be involved in the carcinogenesis of hepatocellular carcinoma (HCC) and some exhibit potential value for oncotherapy. This study was designed to explore the role of miR-346 in the pathogenesis of hepatocellular carcinoma.

METHODS: High throughput screening was employed following with Real time-PCR to investigate the candidate miRNAs. 5-ethynyl-2-deoxyuridine (EdU) assay, CCK-8, transwell assay, cell cycle assay, luciferase reporter assay, western blot and mice xenotransplantation model were performed in the present study.

RESULTS: We found miR-346 was significantly down-regulated in the HCC tissues compared with the non-tumor controls and was associated with the tumor size and TNM grade. Additionally, the in vitro and in vivo assays confirmed that miR-346 suppressed the proliferation of HCC. Then, bioinformatic algorithms and luciferase reporter assays proved that miR-346 directly targeted SET and MYND domain containing 3(SMYD3). We also performed the rescue experiments by inhibiting the expression of SMYD3 and found the down-regulation of SMYD3 could neutralize the inhibitory effects of miR-346 on HCC. At last, the cox proportional hazards analysis showed that low expression of miR-346 was an an independent prognostic factor for HCC.

CONCLUSION: Our findings illuminated miR-346 targeting SMYD3 to inhibit the proliferation of HCC and its down-regulation predicts a poor prognosis.

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PII: 18060

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Research Papers:

MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma

Abstract