PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells

Although mounting evidence has demonstrated that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) can promote tumorigenesis, its role in cancer remains controversial. To find potential target molecules of PGC-1α, GeneFishing<sup>TM</sup> DEG (differentially expressed...

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Main Authors: Jun Gi Cho, Su-Jeong Park, Sang-Heum Han, Joo-In Park
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/1/159
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author Jun Gi Cho
Su-Jeong Park
Sang-Heum Han
Joo-In Park
author_facet Jun Gi Cho
Su-Jeong Park
Sang-Heum Han
Joo-In Park
author_sort Jun Gi Cho
collection DOAJ
description Although mounting evidence has demonstrated that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) can promote tumorigenesis, its role in cancer remains controversial. To find potential target molecules of PGC-1α, GeneFishing<sup>TM</sup> DEG (differentially expressed genes) screening was performed using stable HEK293 cell lines expressing PGC-1α (PGC-1α-HEK293). As results, leucyl-tRNA synthetase 1 (LARS1) was upregulated. Western blot analysis showed that LARS1 was increased in PGC-1α overexpressed SW480 cells but decreased in PGC-1α shRNA knockdown SW620 cells. Several studies have suggested that LARS1 can be a potential target of anticancer agents. However, the molecular network of PGC-1α and LARS1 in human colorectal cancer cells remains unclear. LARS1 overexpression enhanced cell proliferation, migration, and invasion, whereas LARS1 knockdown reduced them. We also observed that expression levels of cyclin D1, c-Myc, and vimentin were regulated by LARS1 expression. We aimed to investigate whether effects of PGC-1α on cell proliferation and invasion were mediated by LARS1. Our results showed that PGC-1α might modulate cell proliferation and invasion by regulating LARS1 expression. These results suggest that LARS1 inhibitors might be used as anticancer agents in PGC-1α-overexpressing colorectal cancer. Further studies are needed in the future to clarify the detailed molecular mechanism by which PGC-1α regulates LARS1 expression.
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spelling doaj.art-0f4c5111656942d79409ab8926c2f1122023-11-16T15:02:25ZengMDPI AGCancers2072-66942022-12-0115115910.3390/cancers15010159PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer CellsJun Gi Cho0Su-Jeong Park1Sang-Heum Han2Joo-In Park3Department of Biochemistry, Dong-A University College of Medicine, Busan 49201, Republic of KoreaDepartment of Biochemistry, Dong-A University College of Medicine, Busan 49201, Republic of KoreaDepartment of Biochemistry, Dong-A University College of Medicine, Busan 49201, Republic of KoreaDepartment of Biochemistry, Dong-A University College of Medicine, Busan 49201, Republic of KoreaAlthough mounting evidence has demonstrated that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) can promote tumorigenesis, its role in cancer remains controversial. To find potential target molecules of PGC-1α, GeneFishing<sup>TM</sup> DEG (differentially expressed genes) screening was performed using stable HEK293 cell lines expressing PGC-1α (PGC-1α-HEK293). As results, leucyl-tRNA synthetase 1 (LARS1) was upregulated. Western blot analysis showed that LARS1 was increased in PGC-1α overexpressed SW480 cells but decreased in PGC-1α shRNA knockdown SW620 cells. Several studies have suggested that LARS1 can be a potential target of anticancer agents. However, the molecular network of PGC-1α and LARS1 in human colorectal cancer cells remains unclear. LARS1 overexpression enhanced cell proliferation, migration, and invasion, whereas LARS1 knockdown reduced them. We also observed that expression levels of cyclin D1, c-Myc, and vimentin were regulated by LARS1 expression. We aimed to investigate whether effects of PGC-1α on cell proliferation and invasion were mediated by LARS1. Our results showed that PGC-1α might modulate cell proliferation and invasion by regulating LARS1 expression. These results suggest that LARS1 inhibitors might be used as anticancer agents in PGC-1α-overexpressing colorectal cancer. Further studies are needed in the future to clarify the detailed molecular mechanism by which PGC-1α regulates LARS1 expression.https://www.mdpi.com/2072-6694/15/1/159PGC-1αleucyl-tRNA synthetase 1 (LARS1)AKTinvasioncolorectal cancer
spellingShingle Jun Gi Cho
Su-Jeong Park
Sang-Heum Han
Joo-In Park
PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
Cancers
PGC-1α
leucyl-tRNA synthetase 1 (LARS1)
AKT
invasion
colorectal cancer
title PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
title_full PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
title_fullStr PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
title_full_unstemmed PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
title_short PGC-1α Regulates Cell Proliferation, Migration, and Invasion by Modulating Leucyl-tRNA Synthetase 1 Expression in Human Colorectal Cancer Cells
title_sort pgc 1α regulates cell proliferation migration and invasion by modulating leucyl trna synthetase 1 expression in human colorectal cancer cells
topic PGC-1α
leucyl-tRNA synthetase 1 (LARS1)
AKT
invasion
colorectal cancer
url https://www.mdpi.com/2072-6694/15/1/159
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