Cargando…
The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway
Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of Acyl-CoA medium-chain synthetase-3 (ACSM3, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation ass...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045751/ https://www.ncbi.nlm.nih.gov/pubmed/33869039 http://dx.doi.org/10.3389/fonc.2021.644840 |
_version_ | 1783678716866461696 |
---|---|
author | Yan, Limei He, Zeping Li, Wei Liu, Ning Gao, Song |
author_facet | Yan, Limei He, Zeping Li, Wei Liu, Ning Gao, Song |
author_sort | Yan, Limei |
collection | PubMed |
description | Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of Acyl-CoA medium-chain synthetase-3 (ACSM3, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation assay, and cell cycle analysis were carried out to investigate cell proliferation ability. Wound healing assay and transwell assay were subsequently used to assess cell migration and invasion. Mice xenografts were then conducted to measure the effects of ACSM3 on tumor development in vivo. Our bioinformatics analysis suggested that the expression of ACSM3 was down-regulated in ovarian cancer tissues, and the low expression level of ACSM3 might related with poorer overall survival than high mRNA expression of ACSM3 in ovarian cancer patients. We artificially regulated the expression of ACSM3 to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of ACSM3 inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of ACSM3 received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by ACSM3 expression. Moreover, ACSM3 overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of ITG β1 (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of ACSM3. And ACSM3 interference obtained the contrary effects in vivo. In summary, ACSM3 acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer. |
format | Online Article Text |
id | pubmed-8045751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80457512021-04-15 The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway Yan, Limei He, Zeping Li, Wei Liu, Ning Gao, Song Front Oncol Oncology Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of Acyl-CoA medium-chain synthetase-3 (ACSM3, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation assay, and cell cycle analysis were carried out to investigate cell proliferation ability. Wound healing assay and transwell assay were subsequently used to assess cell migration and invasion. Mice xenografts were then conducted to measure the effects of ACSM3 on tumor development in vivo. Our bioinformatics analysis suggested that the expression of ACSM3 was down-regulated in ovarian cancer tissues, and the low expression level of ACSM3 might related with poorer overall survival than high mRNA expression of ACSM3 in ovarian cancer patients. We artificially regulated the expression of ACSM3 to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of ACSM3 inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of ACSM3 received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by ACSM3 expression. Moreover, ACSM3 overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of ITG β1 (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of ACSM3. And ACSM3 interference obtained the contrary effects in vivo. In summary, ACSM3 acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer. Frontiers Media S.A. 2021-03-31 /pmc/articles/PMC8045751/ /pubmed/33869039 http://dx.doi.org/10.3389/fonc.2021.644840 Text en Copyright © 2021 Yan, He, Li, Liu and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Yan, Limei He, Zeping Li, Wei Liu, Ning Gao, Song The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title | The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title_full | The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title_fullStr | The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title_full_unstemmed | The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title_short | The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway |
title_sort | overexpression of acyl-coa medium-chain synthetase-3 (acsm3) suppresses the ovarian cancer progression via the inhibition of integrin β1/akt signaling pathway |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045751/ https://www.ncbi.nlm.nih.gov/pubmed/33869039 http://dx.doi.org/10.3389/fonc.2021.644840 |
work_keys_str_mv | AT yanlimei theoverexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT hezeping theoverexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT liwei theoverexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT liuning theoverexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT gaosong theoverexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT yanlimei overexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT hezeping overexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT liwei overexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT liuning overexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway AT gaosong overexpressionofacylcoamediumchainsynthetase3acsm3suppressestheovariancancerprogressionviatheinhibitionofintegrinb1aktsignalingpathway |