LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma
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 hepatocell...
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doaj-c2ef50ea675a43e2ac39a60c4bf0933e2021-01-21T09:27:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.606790606790LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular CarcinomaBaoyong Zhou0Changhong Yang1Xiong Yan2Zhengrong Shi3Heng Xiao4Xufu Wei5Ning Jiang6Zhongjun Wu7Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Bioinformatics, Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Pathology, Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaLeucine 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.https://www.frontiersin.org/articles/10.3389/fonc.2020.606790/fullhepatocellular carcinomaLETM1apoptosisautophagyAMP-activated protein kinase (AMPK)beclin-1/Bcl-2 complex |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Baoyong Zhou Changhong Yang Xiong Yan Zhengrong Shi Heng Xiao Xufu Wei Ning Jiang Zhongjun Wu |
spellingShingle |
Baoyong Zhou Changhong Yang Xiong Yan Zhengrong Shi Heng Xiao Xufu Wei Ning Jiang Zhongjun Wu LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma Frontiers in Oncology hepatocellular carcinoma LETM1 apoptosis autophagy AMP-activated protein kinase (AMPK) beclin-1/Bcl-2 complex |
author_facet |
Baoyong Zhou Changhong Yang Xiong Yan Zhengrong Shi Heng Xiao Xufu Wei Ning Jiang Zhongjun Wu |
author_sort |
Baoyong Zhou |
title |
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma |
title_short |
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma |
title_full |
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma |
title_fullStr |
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma |
title_full_unstemmed |
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma |
title_sort |
letm1 knockdown promotes autophagy and apoptosis through amp-activated protein kinase phosphorylation-mediated beclin-1/bcl-2 complex dissociation in hepatocellular carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-01-01 |
description |
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. |
topic |
hepatocellular carcinoma LETM1 apoptosis autophagy AMP-activated protein kinase (AMPK) beclin-1/Bcl-2 complex |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2020.606790/full |
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