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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01081

The reciprocal interaction between LncRNA CCAT1 and miR-375-3p contribute to the downregulation of IRF5 gene expression by solasonine in HepG2 human hepatocellular carcinoma cells

Zheng Liu1,  Chang Ju Ma1,  Xiao Jun Tang2, Qing Tang2, Li Jie Lou3, Yaya Yu2, Fang Zheng2, Jing Jing Wu2, Xiao-bo Yang4, Wei Wang5 and  Swei S. Hann6*
  • 1Laboratory of Tumor Biology, Guangzhou University of Chinese Medicine, China
  • 2Laboratory of Tumor Biology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, China
  • 3Department of Gastrointestinal Surgery, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, China
  • 4Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, China
  • 5Department of Gastrointestinal Surgery, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, China
  • 6Laboratory of Tumor Biology, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, China

Solasonine (SS), a natural glycoalkaloid component, has been shown potent inhibitory activity and cytotoxicity against many cancer types. However, the precise mechanisms underlying this, particularly in hepatocellular carcinoma (HCC) are poorly understood. In this study, we showed that SS inhibited growth of HCC cells. Mechanistically, we observed that SS increased the expression of miR-375-3p whereas reducing levels of long non-coding RNAs (lncRNAs) CCAT1 was noticed in HepG2 HCC and other cells. In addition, we found that SS repressed transcription factors SP1 and interferon regulatory factor 5 (IRF5) protein expressions. There was a reciprocal interaction among miR-375-3p, CCAT1 and SP1. Moreover, SS inhibited IRF5 promoter activity, which was not observed in cells transfected with excessive expressed SP1 vectors. Interestingly, exogenously expressed IRF5 showed to reverse SS-inhibited CCAT1 and induced-miR-375-3p expressions; and neutralized SS-inhibited growth of HCC cells. Similar results were also found in vivo mouse model. Collectively, our result show that SS inhibits HepG2 HCC growth through the reciprocal regulation between the miR-375-3p and lncRNA CCAT1, this result in transcription factor SP1-mediated reduction of IRF5 expression. The regulations and interactions among miR-375-3p, CCAT1, SP1 and IRF5 axis unveil a novel molecular mechanism underlying the anti-HCC growth by SS. IRF5 may be a potential target for treatment of HCC.

Keywords: solasonine, HCC, IRF5, lncRNA CCAT1, miRNA-375-3p, Sp1

Received: 18 Jun 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Liu, Ma, Tang, Tang, Lou, Yu, Zheng, Wu, Yang, Wang and Hann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Swei S. Hann, Guangzhou University of Chinese Medicine, Laboratory of Tumor Biology, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China, hann2012@outlook.com