作者机构：
[Liu, Ning; Xiang, Shuanglin; Hu, Xiang; Liu, N; Wei, Chenxi; Xiao, Ye; Ding, Xiaofeng] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Liu, Ning; Xiang, Shuanglin; Long, Shengwen; Xun, Yu; Hu, Xiang; Huang, Shulan; Liu, N; Wei, Chenxi; Xiao, Ye; Chen, Wen; Ding, Xiaofeng; Qiu, Feng] Hunan Normal Univ, Coll Life Sci, State Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha 410081, Peoples R China.;[Liu, Ning; Liu, N] Hunan Normal Univ, Sch Med, Key Lab Study & Discovery Small Targeted Mol Huna, Changsha 410013, Peoples R China.;[Xiao, Ye] Cent South Univ, Xiangya Hosp, Endocrinol Res Ctr, Dept Endocrinol, Changsha 410008, Peoples R China.;[Sun, Yi] Cent South Univ, Xiangya Hosp 2, Dept Pathol, Changsha 410011, Peoples R China.
通讯机构：
[Xiang, SL ; Liu, N ; Liu, N] H;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;Hunan Normal Univ, Coll Life Sci, State Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha 410081, Peoples R China.;Hunan Normal Univ, Sch Med, Key Lab Study & Discovery Small Targeted Mol Huna, Changsha 410013, Peoples R China.
关键词：
Hepatocellular carcinoma;Nuclear factor-kappaB;Protein kinase casein kinase II beta;Tumor necrosis factor alpha-induced protein 1;Tumor suppressor
摘要：
Background: Tumor necrosis factor alpha-induced protein 1 (TNFAIP1) is frequently downregulated in cancer cell lines and promotes cancer cell apoptosis. However, its role, clinical significance and molecular mechanisms in hepatocellular carcinoma (HCC) are unknown. Methods: The expression of TNFAIP1 in HCC tumor tissues and cell lines was measured by Western blot and immunohistochemistry. The effects of TNFAIP1 on HCC proliferation, apoptosis, metastasis, angiogenesis and tumor formation were evaluated by Cell Counting Kit-8 (CCK8), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), transwell, tube formation assay in vitro and nude mice experiments in vivo. The interaction between TNFAIP1 and CSNK2B was validated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), Co-immunoprecipitation and Western blot. The mechanism of how TNFAIP1 regulated nuclear factor-kappaB (NF-kappa B) pathway was analyzed by dual-luciferase reporter, immunofluorescence, quantitative Real-time polymerase chain reaction (RT-qPCR) and Western blot. Findings: The TNFAIP1 expression is significantly decreased in HCC tissues and cell lines, and negatively correlated with the increased HCC histological grade. Overexpression of TNFAIP1 inhibits HCC cell proliferation, metastasis, angiogenesis and promotes cancer cell apoptosis both in vitro and in vivo, whereas the knockdown of TNFAIP1 in HCC cell displays opposite effects. Mechanistically, TNFAIP1 interacts with CSNK2B and promotes its ubiquitin-mediated degradation with Cul3, causing attenuation of CSNK2B-dependent NF-kappa B trans-activation in HCC cell. Moreover, the enforced expression of CSNK2B counteracts the inhibitory effects of TNFAIP1 on HCC cell proliferation, migration, and angiogenesis in vitro and in vivo. Interpretation: Our results support that TNFAIP1 can act as a tumor suppressor of HCC by modulating TNFAIP1/CSNK2B/NF-kappa B pathway, implying that TNFAIP1 may represent a potential marker and a promising therapeutic target for HCC. (C) 2019 The Authors. Published by Elsevier B.V.
期刊：
Frontiers in Genetics,2020年11:582905 ISSN：1664-8021
通讯作者：
Wei, Ke;Xiang, SL;Wei, K
作者机构：
[Wei, Chenxi; Xiang, Shuanglin; Tang, Yingxin; Hu, Linmin; Long, Shengwen; Wei, Ke; Xiao, Hui; Gong, Mengting; Xun, Yu] Hunan Normal Univ, Coll Life Sci, Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha, Peoples R China.;[Wei, Ke] Hunan Univ Chinese Med, Med Sch, Changsha, Peoples R China.
通讯机构：
[Xiang, SL ; Wei, K ; Wei, K] H;Hunan Normal Univ, Coll Life Sci, Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha, Peoples R China.;Hunan Univ Chinese Med, Med Sch, Changsha, Peoples R China.
作者机构：
[朱伟; 唐群; 刘春燕] Dept of Pathology, Hunan University of Chinese Medicine, Changsha, 410208, China;[杨胜辉] Dept of Preventive Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[Zeng H.] Dept of Physiology, Hunan University of Chinese Medicine, Changsha, 410208, China;[魏科] Dept of Microbiology, Hunan University of Chinese Medicine, Changsha, 410208, China
期刊：
Frontiers in Genetics,2019年10:456127 ISSN：1664-8021
通讯作者：
Wei, Ke;Xiang, SL;Wei, K
作者机构：
[Wei, Chenxi; Xiang, Shuanglin; Hu, Linming; Long, Shengwen; Wei, Ke; Xiao, Hui; Tang, Yinxing; Gong, Mengting; Xun, Yu] Hunan Normal Univ, Key Lab Prot Chem & Dev Biol Educ, Minist China, Coll Life Sci, Changsha, Hunan, Peoples R China.;[Wei, Ke] Hunan Univ Chinese Med, Med Sch, Changsha, Hunan, Peoples R China.
通讯机构：
[Xiang, SL ; Wei, K ; Wei, K] H;Hunan Normal Univ, Key Lab Prot Chem & Dev Biol Educ, Minist China, Coll Life Sci, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Med Sch, Changsha, Hunan, Peoples R China.
