IFI16 Restoration in Hepatocellular Carcinoma Induces Tumour Inhibition Via Activation of P53 Signals and Inflammasome

Overview

Journal Cell Prolif

Date 2017 Oct 10

PMID 28990231

Citations 24

Authors

Wei Lin

Zhiguang Zhao

Zhonglin Ni

Yaxin Zhao

Wenjun Du

Shijun Chen

Affiliations

Soon will be listed here.

Abstract

Objective: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC).

Materials And Methods: Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1-IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated.

Results: The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up-regulate the p21 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin-α (20 μmol/L). Moreover, IFI16-induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase-1 inhibitor Ac-YVAD-CMK (50 μmol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome.

Conclusion: IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.

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