scholarly journals YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis and migration in ovarian cancer cells

2020 ◽  
Author(s):  
Jie Li ◽  
Lei Wu ◽  
Meili Pei ◽  
Yun Zhang
Keyword(s):  
Ovarian Cancer ◽  
Feedback Loop ◽  
Target Gene ◽  
Epigenetic Modification ◽  
Ovarian Cancer Cells ◽  
Direct Target Gene ◽  
Direct Target ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract RNA methylation can reverse the methylation modification at RNA level, which is a kind of extremely important epigenetic modification. YTHDF2, as a reader of m6A modification, the function and mechanisms of in epithelial ovarian cancer(EOC) have not been elucidated so far. In this study, we demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues, further function studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines, and reduced the global mRNA m6A levels. Next, we found that the expression levels of miR-145 and YTHDF2 were inversely correlated in ovarian cancer tissues and cells, and YTHDF2 is the direct target gene of miR-145. Interestingly, there was a crucial crosstalk between miR-145 and YTHDF2 via a double-negative feedback loop. Overexpression of YTHDF2 rescues miR-145-induced reduction of proliferation and migration in EOC cells. To conclude, YTHDF2 and miR-145, as two crucial m6A regulators, are involved in the progression of EOC by indirectly modulating m6A levels. In view of these promising results, YTHDF2 and miR-145 may provide new insights into the carcinogenesis and new potential therapeutic targets for EOC.

scholarly journals YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Jie Li ◽  
Lei Wu ◽  
Meili Pei ◽  
Yun Zhang
Keyword(s):  
Ovarian Cancer ◽  
Epigenetic Modification ◽  
Ovarian Cancer Cells ◽  
Mrna Levels ◽  
Functional Studies ◽  
Direct Target Gene ◽  
Direct Target ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.

scholarly journals YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

2020 ◽  
Author(s):  
Jie Li ◽  
Lei Wu ◽  
Meili Pei ◽  
Yun Zhang
Keyword(s):  
Ovarian Cancer ◽  
Epigenetic Modification ◽  
Ovarian Cancer Cells ◽  
Mrna Levels ◽  
Functional Studies ◽  
Direct Target Gene ◽  
Direct Target ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.

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

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.

scholarly journals BRDT promotes ovarian cancer cell growth

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Ling Chen ◽  
Shang Cai ◽  
Jing-mei Wang ◽  
Ying-ying Huai ◽  
Pei-Hua Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Scid Mice ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth ◽  
Primary Ovarian Cancer ◽  
And Migration ◽  
Proliferation And Migration

AbstractBromodomain testis-specific factor (BRDT) is a member of the bromodomain and extra-terminal (BET) family proteins. Its expression and potential functions in ovarian cancer were examined. We show that BRDT is overexpressed in human ovarian cancer tissues and in established (CaOV3)/primary ovarian cancer cells. However, its expression is low in ovarian epithelial tissues and cells. Significantly, shRNA-induced silencing or CRISPR/Cas9-mediated knockout of BRDT inhibited ovarian cancer cell growth, viability, proliferation and migration, and induced significant apoptosis activation. Conversely, exogenous overexpression of BRDT, by a lentiviral construct, augmented CaOV3 cell proliferation and migration. In CaOV3 cells expression of two key BRDT target genes, polo-like kinase 1 (PLK1) and aurora kinase C (AURKC), was downregulated by BRDT shRNA or knockout, but upregulated with BRDT overexpression. In vivo, xenograft tumors-derived from BRDT-knockout CaOV3 cells grew significantly slower than control tumors in severe combined immunodeficient (SCID) mice. Furthermore, intratumoral injection of BRDT shRNA lentivirus potently inhibited the growth of primary ovarian cancer xenografts in SCID mice. Downregulation of PLK1 and AURKC was detected in BRDT-knockout and BRDT-silenced tumor tissues. Collectively, BRDT overexpression promotes ovarian cancer cell progression. Targeting BRDT could be a novel strategy to treat ovarian cancer.

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

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0189524 ◽  
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

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

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.

scholarly journals circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

2020 ◽  
Author(s):  
Qin Xu ◽  
Bo Deng ◽  
Manlin Li ◽  
Yang Chen ◽  
Li Zhuan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Competing Endogenous Rnas ◽  
Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

scholarly journals miR-4461 Regulates the Proliferation and Metastasis of Ovarian Cancer Cells and Cisplatin Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Lei Dou ◽  
Yi Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Obvious Effect ◽  
Proliferation And Metastasis ◽  
Direct Target ◽  
Cancer Tissues ◽  
And Control

microRNAs (miRNAs) are of great significance in cancer treatment, which may have a desirable result on the regulation of tumorigenesis, progression, recurrence, and chemo-resistance of ovarian cancer. However, the research on the further potential application of miR-4461 in ovarian cancer is little and limited. Therefore, the study in this paper focus on the investigation of the of miR-4461 in ovarian cancer progression and chemo-resistance. The phenomenon that the proliferation and metastasis of ovarian cancer cells can be promoted by miR4461 is revealed in functional assays. Through the bioinformatics and luciferase reporter analysis, the PTEN is validated to be the direct target of miR-4461 in ovarian. The association between the expression of miR-4461 and PTEN is negative in in human ovarian cancer tissues. The distinction of growth and metastasis capacity between miR-4461 knockdown ovarian cancer cells and control cells is partially abolished by si-PTEN. Moreover, it was found that cisplatin treatment has obvious effect on the miR-4461 knockdown ovarian cancer cells. In summary, the data given in this paper indicate that the miR-4461 can be regarded as a potential onco-miRNA in ovarian cancer by targeting PTEN.

scholarly journals circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

2020 ◽  
Author(s):  
Qin Xu ◽  
Bo Deng ◽  
Manlin Li ◽  
Yang Chen ◽  
Li Zhuan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Competing Endogenous Rnas ◽  
Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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