AUTHOR=Yan Limei , He Zeping , Li Wei , Liu Ning , Gao Song 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.644840

DOI=10.3389/fonc.2021.644840

ISSN=2234-943X

ABSTRACT=<p>Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of <italic>Acyl-CoA medium-chain synthetase-3</italic> (<italic>ACSM3</italic>, 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 <italic>ACSM3</italic> on tumor development <italic>in vivo</italic>. Our bioinformatics analysis suggested that the expression of <italic>ACSM3</italic> was down-regulated in ovarian cancer tissues, and the low expression level of <italic>ACSM3</italic> might related with poorer overall survival than high mRNA expression of <italic>ACSM3</italic> in ovarian cancer patients. We artificially regulated the expression of <italic>ACSM3</italic> to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of <italic>ACSM3</italic> inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of <italic>ACSM3</italic> received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by <italic>ACSM3</italic> expression. Moreover, <italic>ACSM3</italic> overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of <italic>ITG β1</italic> (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of <italic>ACSM3</italic>. And <italic>ACSM3</italic> interference obtained the contrary effects <italic>in vivo</italic>. In summary, <italic>ACSM3</italic> acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer.</p>