Open AccessIFI 16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome
Author(s) -
Lin Wei,
Zhao Zhiguang,
Ni Zhonglin,
Zhao Yaxin,
Du Wenjun,
Chen Shijun
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12392
Subject(s) - apoptosis , biology , inflammasome , cancer research , in vivo , transfection , programmed cell death , hepatocellular carcinoma , carcinogenesis , cell culture , cell growth , cell , microbiology and biotechnology , cancer , immunology , inflammation , biochemistry , genetics
Abstract Objective Interferon‐inducible 16 ( IFI 16) 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 IFI 16 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 IFI 16. After the transfection of pc DNA 3.1‐ IFI 16 into Huh7 and SMMC 7721 cells in vitro, the influence of IFI 16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI 16 in vivo was further investigated. Results The expression of IFI 16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI 16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI 16 could activate p53 at Ser15 to up‐regulate the p21 WAF 1/ CIP 1 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin‐α (20 μmol/L). Moreover, IFI 16‐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 IFI 16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome. Conclusion IFI 16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.