Abstract
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.
Highlights
Ovarian cancer is considered one of the most fatal gynecologic malignancies [1]
The results showed that ACSM3 was markedly low expressed in ovarian cancer tissues than normal tissues (Figure 1A) Survival analysis revealed that the low expression level of ACSM3 was related with poorer overall survival than high mRNA expression of ACSM3 in 424 ovarian cancer patients, suggesting the prognostic significance of ACSM3. (Figure 1B)
Our results suggested the possibility that ACSM3 attenuated the expression of cell proliferation or metastasis-related proteins by the inhibition of the Integrin b1/AKT signaling pathway in ovarian cancer
Summary
Due to the asymptomatic development, ovarian cancer is frequently not diagnosed until at an advanced and incurable stage, which is seen as a silent killer [2]. When ovarian cancer is diagnosed at an early stage that grows in one or two sides of ovaries, the cure rate of it could reach 90% [3]. The ACSM3 Suppresses the Ovarian Cancer cure rate of ovarian cancer attenuates substantially with the metastasis of the tumors to the uterus and bladder (stage II), the peritoneal cavity (stage III), or the visceral organs (stage IV) [3]. More than 70% of patients with ovarian cancer are not diagnosed until tumors are actively metastasized and developed to stage III or IV [4]. Ovarian cancer tumors compress the visceral organs and even spread to the parenchyma of the lung or liver [5]. It is essential to find new potential target for effectual therapy in ovarian cancer
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