ATXN7L3 positively regulates SMAD7 transcription in hepatocellular carcinoma with growth inhibitory function.
ATXN7L3 positively regulates SMAD7 transcription in hepatocellular carcinoma with growth inhibitory function.
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ATXN7L3在肝细胞癌中正向调节SMAD7转录，具有生长抑制功能。
DOI：
10.1016/j.ebiom.2020.103108
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发表时间：
2020-12
期刊：
影响因子：
11.1
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Sun N;Zhong X;Wang S;Zeng K;Sun H;Sun G;Zou R;Liu W;Liu W;Lin L;Song H;Lv C;Wang C;Zhao Y
肝细胞癌（HCC）是世界范围内癌症死亡的主要原因，对药物治疗的需求尚未得到满足。ATXN7L3在HCC进展中的功能尚不清楚。采用RNA测序、实时荧光定量PCR和western blot检测基因表达。采用染色质免疫沉淀法检测可能的机制。免疫组化染色检测蛋白表达。通过集落形成、细胞生长曲线和异种移植物肿瘤实验，观察细胞在体外和体内的生长情况。ATXN7L3在HCC细胞中作为er α介导的转激活的辅助激活因子，从而促进SMAD7转录的增强。ATXN7L3被募集到SMAD7基因的启动子区域，从而调控组蛋白H2B泛素化水平，增强SMAD7的转录。鉴定出一系列受ATXN7L3调控的基因。此外，ATXN7L3参与抑制肿瘤生长。此外，ATXN7L3在HCC样本中表达较低，且ATXN7L3的低表达与HCC患者临床预后较差呈正相关。本研究表明，ATXN7L3是SMAD7转录的一种新型调节剂，随后参与HCC中肿瘤生长的抑制，这为ATXN7L3在HCC进展中的未知作用提供了支持。基金资助：国家科技部973项目（2013CB945201）、国家自然科学基金（31871286、81872015、31701102、81702800、81902889）、辽宁省特任教授基金、辽宁省自然科学基金（20180530072）；中国博士后科学基金（2019M651164）。
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with unmet need for the pharmacological therapy. The functions of ATXN7L3 in HCC progression are not known. RNA sequence, quantitative real-time PCR, and western blot were performed to detect gene expression. Chromatin immunoprecipitation was performed to detect possible mechanisms. Immunohistochemical stain was performed to examine the protein expression. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth in vitro and in vivo. ATXN7L3 functions as a coactivator for ERα-mediated transactivation in HCC cells, thereby contributing to enhanced SMAD7 transcription. ATXN7L3 is recruited to the promoter regions of SMAD7 gene, thereby regulating histone H2B ubiquitination level, to enhance the transcription of SMAD7. A series of genes regulated by ATXN7L3 were identified. Moreover, ATXN7L3 participates in suppression of tumor growth. In addition, ATXN7L3 is lower expressed in HCC samples, and the lower expression of ATXN7L3 positively correlates with poor clinical outcome in patients with HCC. This study demonstrated that ATXN7L3 is a novel regulator of SMAD7 transcription, subsequently participating in inhibition of tumor growth in HCC, which provides an insight to support a previously unknown role of ATXN7L3 in HCC progression. This work was funded by 973 Program Grant from the Ministry of Science and Technology of China (2013CB945201), National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, Natural Science Foundation of Liaoning Province (No.20180530072); China Postdoctoral Science Foundation (2019M651164).
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影响因子：
29.4
作者：
Liu, Wan-Hsin;Yeh, Shiou-Hwei;Chen, Pei-Jer
通讯作者：
Chen, Pei-Jer
影响因子：
12.3
作者：
Lin CY;Ström A;Vega VB;Kong SL;Yeo AL;Thomsen JS;Chan WC;Doray B;Bangarusamy DK;Ramasamy A;Vergara LA;Tang S;Chong A;Bajic VB;Miller LD;Gustafsson JA;Liu ET
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Liu ET
DOI：
10.1073/pnas.96.5.1858
发表时间：
1999-03-02
影响因子：
11.1
作者：
Nawaz, Z;Lonard, DM;O'Malley, BW
通讯作者：
O'Malley, BW
影响因子：
16
作者：
Gao WW;Xiao RQ;Zhang WJ;Hu YR;Peng BL;Li WJ;He YH;Shen HF;Ding JC;Huang QX;Ye TY;Li Y;Liu ZY;Ding R;Rosenfeld MG;Liu W
通讯作者：
Liu W
影响因子：
4.8
作者：
Daniel, JA;Torok, MS;Grant, PA
通讯作者：
Grant, PA