Oncotarget

Research Papers:

MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma

Shaohui Tang, Yanfang Chen, Shufen Feng, Tingzhuang Yi, Xuyou Liu, Qiang Li, Zhilong Liu, Cuiping Zhu, Jianjun Hu, Xi Yu, Min Wang, Guoli Cao, Hui Tang, Caiqun Bie, Feng Ma, Huijun Tang, Gang Du and Jianwei Huang _

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Oncotarget. 2017; 8:99871-99888. https://doi.org/10.18632/oncotarget.21737

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Abstract

Shaohui Tang1,*, Yanfang Chen1,*, Shufen Feng1,*, Tingzhuang Yi2,*, Xuyou Liu3,*, Qiang Li4, Zhilong Liu4, Cuiping Zhu1, Jianjun Hu1, Xi Yu1, Min Wang1, Guoli Cao1, Hui Tang5, Caiqun Bie6, Feng Ma1, Huijun Tang6, Gang Du5 and Jianwei Huang3

1Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China

2Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationlities, Baise, Guangxi, China

3Department of Gastroenterology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

4Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China

5Clinical Medicine Research Institute, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China

6Department of Gastroenterology, The Affiliated Shenzhen Shajing Hospital, Guangzhou Medical University, Shenzhen, Guangdong, China

*These authors contributed equally to this work

Correspondence to:

Jianwei Huang, email: [email protected]

Shaohui Tang, email: [email protected]

Keywords: miRNAs, transcription regulation, ago proteins, liver cancer, inferior clinical outcome

Received: August 01, 2017     Accepted: September 22, 2017     Published: October 11, 2017

ABSTRACT

The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5′-untranslated region (5′UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5′UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5′UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.


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