TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer

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.

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MicroRNA-301a Promotes Cell Proliferation and Resistance to Apoptosis through PTEN/PI3K/Akt Signaling Pathway in Human Ovarian Cancer

Gynecologic and Obstetric Investigation ◽

10.1159/000513070 ◽

2021 ◽

pp. 1-9

Author(s):

Jie Ni ◽

Ying Chen ◽

Beibei Fei ◽

Yan Zhu ◽

Yibei Du ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Critical Role ◽

Akt Signaling ◽

Ovarian Cancer Cells ◽

Control Group ◽

Akt Signaling Pathway

Background: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. Objective: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. Methods: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. Results: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. Conclusion: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.

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MicroRNA-196a promotes cell proliferation and inhibits apoptosis in human ovarian cancer by directly targeting DDX3 and regulating the PTEN/PI3K/AKT signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2020.11236 ◽

2020 ◽

Vol 22 (2) ◽

pp. 1277-1284 ◽

Cited By ~ 1

Author(s):

Jie Ni ◽

Li Chen ◽

Li Ling ◽

Mengfei Wu ◽

Qiongzhen Ren ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Human Ovarian Cancer ◽

Akt Signaling Pathway

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TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway

Journal of Translational Medicine ◽

10.1186/s12967-021-02781-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Tianshui Sun ◽

Fangfang Bi ◽

Zhuonan Liu ◽

Qing Yang

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Mrna Expression ◽

Signaling Pathway ◽

Akt Signaling ◽

Biological Behavior ◽

Akt Signaling Pathway ◽

Invasion And Migration ◽

Potential Biomarker ◽

And Migration

Abstract Background Ovarian cancer (OV) is the deadliest gynecological cancer. Transmembrane protein 119 (TMEM119) has been reported as oncogene in several human cancers. However, the function of TMEM119 in OV is still poorly known. Methods Western blot and qRT-PCR were used to analyze TMEM119 levels. Transwell assays, wound healing assays, CCK-8 assays and EdU cell proliferation assays were designed to explore the function and potential mechanism of TMEM119 in malignant biological behaviors in OV. Results TMEM119 was observed to be overexpressed in OV tissues and associated with poor survival in OV patients. Knockdown and overexpression experiments demonstrated that TMEM119 promoted proliferation, invasion, and migration in OV cells in vitro. TMEM119 mRNA expression was related to the pathways of focal adhesion according to Gene Set Enrichment Analyses and was correlated with the mRNA expression level of platelet-derived growth factor receptor beta (PDGFRB). TMEM119 exerted oncogenic effects partially by regulating the expression of PDGFRB and by activating the PI3K/AKT signaling pathway. Conclusions Collectively, our findings highlight the potential role of TMEM119 in the malignant biological behavior of OV, which may serve as a potential biomarker and a therapeutic candidate for OV.

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microRNA184 Reverses Cisplatin Resistance in Human Ovarian Cancer Cells by Regulating the Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2214 ◽

2020 ◽

Vol 10 (1) ◽

pp. 115-120

Author(s):

Ping Liu ◽

Jie Wen ◽

Nannan Zhao

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Caspase 3 ◽

Cisplatin Resistance ◽

Akt Signaling ◽

Akt Signaling Pathway

Ovarian cancer is prone to drug resistance, resulting in poor prognosis. microRNA184 plays a role in many diseases such as tumor and inflammation, but whether microRNA184 regulates ovarian cancer cisplatin resistance is unknown. The ovarian cancer SKOV3 cell line and cisplatin-resistant strain cell SKOV3/DDP were cultured and microRNA184 expression was analyzed by Real time PCR. Transfection of microRNA184 siRNA into SKOV3/DDP under ly294002 (PI3K/AKT inhibitor) treatment followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, cell migration by cell scratch assay, levels of Bax and Bcl-2 by Real time PCR and PI3K/AKT signaling by Western blot. microRNA184 expression was significantly increased in SKOV3/DDP cells compared to SKOV3 cells (P < 0.05). microRNA184 siRNA can significantly down-regulate microRNA184 expression in SKOV3/DDP, inhibit cell proliferation, increase Caspase 3 activity, inhibit cell migration, increase Bax expression, decrease Bcl-2 and decrease pAKT expression (P < 0.05). Addition of ly294002 further significantly promoted the above changes (P < 0.05). Targeting microRNA184 can inhibit SKOV3/DDP cell apoptosis by inhibiting PI3K/AKT signaling pathway, decrease tumor cell proliferation and migration, and inhibit the occurrence and development of cisplatin-resistant ovarian cancer.

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MiR-198 inhibits proliferation, invasion and migration of ovarian cancer cells by regulating the PI3K/Akt signaling pathway

Acta Biochimica Polonica ◽

10.18388/abp.2020_5546 ◽

2021 ◽

Author(s):

Huichao Xiao ◽

Yafeng Zheng ◽

Jiming Chen ◽

Huaji Shen

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Ovarian Cancer Cells ◽

Akt Signaling Pathway ◽

Tissue Samples ◽

Invasion And Migration ◽

And Migration ◽

The Impact

Objective: The specific objective of this investigation is to explore the impact of miR-198 on proliferation, migration as well as invasion of ovarian cancer (OC) cells. Methods: OC tissue and adjacent normal tissue samples from OC patients were collected, and normal human ovarian epithelial cell IOSE80 and OC cell lines SKOV3, Caov3, A2780 and OVCAR3 were selected in this study for investigation. MiR-198 expression level was assessed using RT-qPCR. MTT, colony formation assay, Transwell and wound healing assay, and flow cytometry were adopted to analyze the role of miR-198 in OVCAR cell proliferation, invasion, migration, as well as apoptosis. Meanwhile, the levels of P13K/Akt signaling pathway-related proteins were determined by western blotting. Results: A significant decrease in miR-198 level was revealed in the OC tissues and cells, contributing to the promotion of OVCAR3 cells in terms of proliferation, migration, invasion, and inhibition of apoptosis. MiR-198 overexpression had an opposite effect on these biological processes of OVCAR3 cells. Further study found that down-regulation of miR-198 caused a significant increase in the activity of PI3K/Akt signaling pathway in the OVCAR3 cells. In contrast, overexpressed miR-198 led to inhibition of this pathway’s activity. Conclusion: MiR-198 may possess an ability to inhibit activation of the P13K/Akt pathway, thus suppressing the OC cell proliferation, migration, as well as invasion.

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