Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation
Abstract Solute carrier family 25 member 20 (SLC25A20) is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation. A previous-integrated-proteogenomic study had identified SLC25A20 as one of the top-three prognostic biomarkers in H...
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doaj-35fefbca1039403fbc6b64be9340105c2021-04-11T11:05:25ZengNature Publishing GroupCell Death and Disease2041-48892021-04-0112411210.1038/s41419-021-03648-1Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidationPeng Yuan0Jiao Mu1Zijun Wang2Shuaijun Ma3Xiuwei Da4Jian Song5Hongxin Zhang6Le Yang7Jibin Li8Jingyue Yang9Department of Pain Treatment, Tangdu Hospital, Air Force Military Medical UniversityDepartment of Hematology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Pain Treatment, Tangdu Hospital, Air Force Military Medical UniversityDepartment of Urology, Xijing Hospital, Air Force Military Medical UniversityDepartment of Pain Treatment, Tangdu Hospital, Air Force Military Medical UniversityDepartment of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical UniversityDepartment of Pain Treatment, Tangdu Hospital, Air Force Military Medical UniversityPrecision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Air Force Military Medical UniversityState Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology, Air Force Military Medical UniversityDepartment of Oncology, Xijing Hospital, Air Force Military Medical UniversityAbstract Solute carrier family 25 member 20 (SLC25A20) is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation. A previous-integrated-proteogenomic study had identified SLC25A20 as one of the top-three prognostic biomarkers in HCC. However, the expression and the biological function of SLC25A20 have not yet been investigated in HCC. In the present study, we found that SLC25A20 expression is frequently down-regulated in HCC cells mainly due to the up-regulation of miR-132-3p. Down-regulation of SLC25A20 is associated with a poor prognosis in patients with HCC. SLC25A20 suppressed HCC growth and metastasis, both in vitro and in vivo, by suppression of G1–S cell transition, epithelial-to-mesenchymal transition (EMT), and induction of cell apoptosis. Mechanistically, SLC25A20 down-regulation promoted HCC growth and metastasis through suppression of fatty-acid oxidation. Altogether, SLC25A20 plays a critical tumor-suppressive role in carcinogenesis of HCC; SLC25A20 may serve as a novel prognostic factor and therapeutic target for patients with HCC.https://doi.org/10.1038/s41419-021-03648-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peng Yuan Jiao Mu Zijun Wang Shuaijun Ma Xiuwei Da Jian Song Hongxin Zhang Le Yang Jibin Li Jingyue Yang |
spellingShingle |
Peng Yuan Jiao Mu Zijun Wang Shuaijun Ma Xiuwei Da Jian Song Hongxin Zhang Le Yang Jibin Li Jingyue Yang Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation Cell Death and Disease |
author_facet |
Peng Yuan Jiao Mu Zijun Wang Shuaijun Ma Xiuwei Da Jian Song Hongxin Zhang Le Yang Jibin Li Jingyue Yang |
author_sort |
Peng Yuan |
title |
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
title_short |
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
title_full |
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
title_fullStr |
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
title_full_unstemmed |
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
title_sort |
down-regulation of slc25a20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-04-01 |
description |
Abstract Solute carrier family 25 member 20 (SLC25A20) is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation. A previous-integrated-proteogenomic study had identified SLC25A20 as one of the top-three prognostic biomarkers in HCC. However, the expression and the biological function of SLC25A20 have not yet been investigated in HCC. In the present study, we found that SLC25A20 expression is frequently down-regulated in HCC cells mainly due to the up-regulation of miR-132-3p. Down-regulation of SLC25A20 is associated with a poor prognosis in patients with HCC. SLC25A20 suppressed HCC growth and metastasis, both in vitro and in vivo, by suppression of G1–S cell transition, epithelial-to-mesenchymal transition (EMT), and induction of cell apoptosis. Mechanistically, SLC25A20 down-regulation promoted HCC growth and metastasis through suppression of fatty-acid oxidation. Altogether, SLC25A20 plays a critical tumor-suppressive role in carcinogenesis of HCC; SLC25A20 may serve as a novel prognostic factor and therapeutic target for patients with HCC. |
url |
https://doi.org/10.1038/s41419-021-03648-1 |
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