LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma.
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma.
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LETM1 敲低通过 AMP 激活蛋白激酶磷酸化介导的肝细胞癌中 Beclin-1/Bcl-2 复合体解离促进自噬和细胞凋亡
DOI：
10.3389/fonc.2020.606790
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发表时间：
2020
影响因子：
4.7
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Zhou B;Yang C;Yan X;Shi Z;Xiao H;Wei X;Jiang N;Wu Z
Leucine zipper/EF hand-containing transmembrane-1（LETM 1）是一种线粒体内膜蛋白，参与多种原发性肿瘤的发生和发展，可能参与多种生物学过程。然而，LETM 1在肝细胞癌（HCC）进展中的生物学作用和分子机制仍不清楚。在这项研究中，我们发现LETM 1在HCC组织和细胞系中高度表达，并且较高的LETM 1表达与HCC患者较低的总生存率相关。此外，LETM 1的敲低抑制Huh 7和QGY-7701肝癌细胞系的增殖并增强凋亡和自噬。从机制上讲，LETM 1的敲除通过AMPK和Bcl-2的磷酸化来解离Beclin-1/Bcl-2复合物。这些结果表明，LETM 1参与了肝癌的发展，并可能成为一个新的治疗肝癌的目标。
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an inner mitochondrial membrane protein that has been reported to be involved in many primary tumors and may regulate many biological processes. However, the biological role and molecular mechanism of LETM1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that LETM1 was highly expressed in HCC tissues and cell lines and that higher LETM1 expression was associated with a lower overall survival rate in HCC patients. In addition, knockdown of LETM1 inhibited proliferation and enhanced apoptosis and autophagy in the Huh 7 and QGY-7701 liver cancer cell lines. Mechanistically, knockdown of LETM1 dissociated the Beclin-1/Bcl-2 complex through phosphorylation of AMPK and Bcl-2. These results demonstrated that LETM1 is involved in the development of HCC and could be a novel therapeutic target in HCC.
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影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
影响因子：
10.3
作者：
Ordoñez R;Fernández A;Prieto-Domínguez N;Martínez L;García-Ruiz C;Fernández-Checa JC;Mauriz JL;González-Gallego J
通讯作者：
González-Gallego J
影响因子：
13.5
作者：
Heimbach, Julie K.;Kulik, Laura M.;Marrero, Jorge A.
通讯作者：
Marrero, Jorge A.
影响因子：
4.2
作者：
Owada, Satoshi;Endo, Hitoshi;Tatemichi, Masayuki
通讯作者：
Tatemichi, Masayuki
AMPK：代谢和线粒体稳态的监护人。
DOI：
10.1038/nrm.2017.95
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Herzig S;Shaw RJ
通讯作者：
Shaw RJ