USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.
USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.
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usf2介导的TXNRD1上调通过激活Akt/mTOR信号通路参与肝细胞癌的进展。
DOI：
10.1038/s41419-022-05363-x
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发表时间：
2022-11-01
影响因子：
9
通讯作者：
Dong, Ke-Shuai
中科院分区：
文献类型：
--
作者：
Huang, Wen-Ya;Liao, Zhi-Bin;Zhang, Jia-Cheng;Zhang, Xin;Zhang, Hong-Wei;Liang, Hui-Fang;Zhang, Zun-Yi;Yang, Tao;Yu, Jia;Dong, Ke-Shuai
Thioredoxin reductase 1 (TXNRD1) is one of the major redox regulators in mammalian cells, which has been reported to be involved in tumorigenesis. However, its roles and regulatory mechanism underlying the progression of HCC remains poorly understood. In this study, we demonstrated that TXNRD1 was significantly upregulated in HCC tumor tissues and correlated with poor survival in HCC patients. Functional studies indicated TXNRD1 knockdown substantially suppressed HCC cell proliferation and metastasis both in vitro and in vivo, and its overexpression showed opposite effects. Mechanistically, TXNRD1 attenuated the interaction between Trx1 and PTEN which resulting in acceleration of PTEN degradation, thereby activated Akt/mTOR signaling and its target genes which conferred to elevated HCC cell mobility and metastasis. Moreover, USF2 was identified as a transcriptional suppressor of TXNRD1, which directly interacted with two E-box sites in TXNRD1 promoter. USF2 functioned as tumor suppressor through the downstream repression of TXNRD1. Further clinical data revealed negative co-expression correlations between USF2 and TXNRD1. In conclusion, our findings reveal that USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.
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影响因子：
11.2
作者：
Dai B;Yoo SY;Bartholomeusz G;Graham RA;Majidi M;Yan S;Meng J;Ji L;Coombes K;Minna JD;Fang B;Roth JA
通讯作者：
Roth JA
影响因子：
5.7
作者：
Hu, Jing;Zhang, Huijuan;Fang, Bingliang
通讯作者：
Fang, Bingliang
影响因子：
5.3
作者：
Jiang, B;Mendelson, CR
通讯作者：
Mendelson, CR
影响因子：
8
作者：
Dong, Ke-shuai;Chen, Yan;Dong, Han-hua
通讯作者：
Dong, Han-hua
DOI：
10.1152/ajpgi.00312.2004
发表时间：
2005-06-01
影响因子：
4.5
作者：
Hadjiagapiou, C;Borthakur, A;Dudeja, PK
通讯作者：
Dudeja, PK