Mechanism of resistin-induced enhancement of proliferation and migration of ovarian cancer cells

Archives of Medical Science ◽

10.5114/aoms.2020.100652 ◽

2020 ◽

Author(s):

Li Pang ◽

Xian-li Li

Keyword(s):

Ovarian Cancer ◽

Wound Healing ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Ovarian Epithelial Carcinoma ◽

And Migration ◽

Proliferation And Migration

IntroductionResistin, a novel hormone secreted by human adipocytes and mononuclear cells, is associated with obesity, insulin resistance, and inflammation. Recent studies showed that resistin plays a key role in ovarian cancer cells. In this study, we investigated the potential of resistin to regulate the proliferation and migration of ovarian cancer cells.Material and methodsA series of in vitro functional experiments were carried out to elucidate the role of resistin in ovarian cancer progression and the molecular mechanisms underlying its role.ResultsResistin enhanced the proliferation of human ovarian epithelial carcinoma cells (HO-8910) in a time- and dose-dependent manner (30–100 ng/ml). Furthermore, HO-8910 cells cultured in adipocyte-conditioned medium showed dramatically increased rates of proliferation. Resistin knockout during adipocyte culture attenuated the proliferation of HO-8910 cells treated with adipocyte-conditioned media, indicating that resistin may promote HO-8910 cell proliferation via the mechanistic target of a rapamycin (mTOR)-mediated signaling pathway. Resistin (30–100 ng/ml) also enhanced wound-healing rates in a time- and concentration-dependent manner. Co-culturing HO-8910 cells with adipocytes also increased the wound-healing rates. Resistin expression was inhibited by miR-124-1 transcriptional activity, and resistin-mediated HO-8910 cell migration was also regulated by miR-124-1. Furthermore, we also confirmed the role of resistin in promoting tumor growth in vivo.ConclusionsThese findings suggest that resistin may serve as an effective therapeutic target for ovarian epithelial carcinoma, especially in patients who are obese.

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Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells

10.1101/2020.04.17.042382 ◽

2020 ◽

Author(s):

Fatma Aysun Turut ◽

Hilal Acidereli ◽

Ozge Cevik

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

The Novel ◽

Cxcl12 Expression ◽

Protein Expressions ◽

Cox 2 ◽

And Migration ◽

Proliferation And Migration

AbstractMicroRNAs are important regulators in the growth and metastasis of ovarian cancers. Many assays were established to identify the role of miR-144-3p in ovarian cancer cells and its interaction with COX-2 and chemokines (CXCR4 and CXCL12). The ovarian cancer cells (OVCAR-3 and SKOV-3) were transfected with Anti-miR-144 to downregulate the miR-144-3p and cultured for 36 h. We herein examined the cell viability, colony formation, cell migration, COX-2 reporter activity, the protein expressions of CXCR4, CXCL12, COX-2, VEGF, Caspase-3, BAX and Bcl-2. We have observed that the suppression of miR-144-3p significantly increased the cell proliferation and migration and decreased the apoptosis. Moreover, the downregulation of miR-144-3p markedly increased the COX-2, CXCR4, CXCL12 and VEGF expression in OVCAR-3 and SKOV-3 ovarian cancer cells. In conclusion, miR-144-3p may play important roles in the regulation of chemokine receptor CXCR4 and its ligand CXCL12 in the progressive ovarian tumors expressing COX2. These data suggests that miR-144 has the novel therapeutic targets for the cancer therapy and cancer prevention.

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Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src

PLoS ONE ◽

10.1371/journal.pone.0189524 ◽

2018 ◽

Vol 13 (1) ◽

pp. e0189524 ◽

Cited By ~ 7

Author(s):

Mian M. K. Shahzad ◽

Mildred Felder ◽

Kai Ludwig ◽

Hannah R. Van Galder ◽

Matthew L. Anderson ◽

...

Keyword(s):

Ovarian Cancer ◽

Linoleic Acid ◽

Er Stress ◽

Cancer Cells ◽

Conjugated Linoleic Acid ◽

Ovarian Cancer Cells ◽

And Migration ◽

Proliferation And Migration

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Sepiapterin inhibits cell proliferation and migration of ovarian cancer cells via down-regulation of p70S6K-dependent VEGFR-2 expression

Oncology Reports ◽

10.3892/or.2011.1335 ◽

2011 ◽

Cited By ~ 1

Author(s):

Shin Choi

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Down Regulation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246

Cell Death Discovery ◽

10.1038/s41420-021-00600-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xuehan Bi ◽

Xiao Lv ◽

Dajiang Liu ◽

Hongtao Guo ◽

Guang Yao ◽

...

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

High Expression ◽

Ovarian Cancer Cells ◽

Inadequate Knowledge ◽

And Migration ◽

Cancer Tissues

AbstractOvarian cancer is a common gynecological malignant tumor with a high mortality rate and poor prognosis. There is inadequate knowledge of the molecular mechanisms underlying ovarian cancer. We examined the expression of methyltransferase-like 3 (METTL3) in tumor specimens using RT-qPCR, immunohistochemistry, and Western blot analysis, and tested the methylation of METTL3 by MSP. Levels of METTL3, miR-1246, pri-miR-1246 and CCNG2 were then analyzed and their effects on cell biological processes were also investigated, using in vivo assay to validate the in vitro findings. METTL3 showed hypomethylation and high expression in ovarian cancer tissues and cells. Hypomethylation of METTL3 was pronounced in ovarian cancer samples, which was negatively associated with patient survival. Decreased METTL3 inhibited the proliferation and migration of ovarian cancer cells and promoted apoptosis, while METTL3 overexpression exerted opposite effects. Mechanistically, METTL3 aggravated ovarian cancer by targeting miR-1246, while miR-1246 targeted and inhibited CCNG2 expression. High expression of METTL3 downregulated CCNG2, promoted the metabolism and growth of transplanted tumors in nude mice, and inhibited apoptosis. The current study highlights the promoting role of METTL3 in the development of ovarian cancer, and presents new targets for its treatment.

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Expression of Mitochondrial Progesterone Receptor (PR-M) in Ovarian Cancer and Its Effect on Cell Metastasis Induced by Progesterone

10.21203/rs.3.rs-285751/v1 ◽

2021 ◽

Author(s):

Qingqing Yang ◽

Chang Duan ◽

Haofan Wang ◽

Dongyuan Jiang ◽

Yaping Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Progesterone Receptor ◽

Cancer Cells ◽

Cell Lines ◽

Ovarian Tumors ◽

Ovarian Cancer Cells ◽

Borderline Tumor ◽

And Migration ◽

Cancer Tissues ◽

Proliferation And Migration

Abstract Background: PR-M refers to a novel truncated progesterone receptor located on the outer membrane of mitochondria, capable of facilitating the proliferation of leiomyoma cells and breast cancer cells, as well as inhibiting apoptosis as impacted by progesterone or progesterone agonists. However, its role in ovarian tumors has not yet been elucidated.Objective: To study the expression of PR-M in different ovarian tumor tissues and normal tissues, and the effect exerted by progesterone on the proliferation and migration of SKOV-3 cells that achieve high PR-M expression.Methods: Real- time PCR and Western blot were employed for determining PR-M levels in cell lines, non-cancer tissues and ovarian cancer tissues. By immunohistochemistry, PR-M protein expression in benign tumor, borderline tumor and epithelial carcinoma was detected, and the clinicopathological characteristics between PR-M and cancer were analyzed. Furthermore, CCK-8 and scratch test were performed to explore the proliferation and migration of SKOV-3 cells exhibiting high PR-M expression.Results: PR-M increased significantly in cancer tissues and ovarian cancer cell lines, in comparison to normal cells and non-cancer tissues. The abnormal expression showed a significant correlation with intraperitoneal metastasis, lymph node metastasis, clinically related stage and CA125 level, suggesting that high PR-M expression may affect the progression of ovarian tumors. During the cell experiment, PR-M achieved the maximum expression in SKOV-3 cells (PR-A / B(-)). As impacted by progesterone, SKOV-3 cells (PR-A / B(-)) achieved the enhanced proliferation and migration. Besides, the enhancing effect was dose and time-dependent.Conclusion: PR-M is critical to develop ovarian cancer. Progesterone may facilitate the proliferation and migration of ovarian cancer cells exhibiting high PR-M expression.

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UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00877-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Wenjing Hu ◽

Min Li ◽

Youguo Chen ◽

Xinxian Gu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Xenograft Model ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Cancer Proliferation ◽

Skov3 Cells

Abstract Background Ovarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear. Materials and methods In this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model. Results The results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner. Conclusions These data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

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