MiR-98-3p regulates ovarian granulosa cell proliferation and apoptosis in polycystic ovary syndrome by targeting YY1

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood. Methods To clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS. Results miR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells. Conclusions miR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.

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Roles of different n-3/n-6 PUFA ratios in ovarian cell development and steroidogenesis in PCOS rats

Food & Function ◽

10.1039/c9fo01730e ◽

2019 ◽

Vol 10 (11) ◽

pp. 7397-7406 ◽

Cited By ~ 1

Author(s):

Xiaoshu Ma ◽

Xuechun Weng ◽

Xusong Hu ◽

Qiaozhi Wang ◽

Ye Tian ◽

...

Keyword(s):

Cell Proliferation ◽

Polycystic Ovary Syndrome ◽

Granulosa Cell ◽

Polycystic Ovary ◽

Growth Arrest ◽

Cell Development ◽

Follicle Growth ◽

Ovary Syndrome ◽

Ovarian Cell ◽

Endocrine Disorder

Polycystic ovary syndrome (PCOS) is a complex and common endocrine disorder characterized by hyperandrogenism, which is accompanied by follicle growth arrest at the small antral stage, minimal granulosa cell proliferation, and chronic anovulation.

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The LINC00477/miR-128 axis promotes the progression of polycystic ovary syndrome by regulating ovarian granulosa cell proliferation and apoptosis

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00718-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Haijie Gao ◽

Jinna Jiang ◽

Yingying Shi ◽

Jiying Chen ◽

Lijian Zhao ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Granulosa Cells ◽

Polycystic Ovary ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Serum Samples ◽

Ovary Syndrome ◽

Ovarian Granulosa Cell ◽

Proliferation And Apoptosis ◽

And Migration

Abstract Background Long noncoding RNAs (lncRNAs) participate in the pathogenesis of various human diseases. This study aims to investigate the roles of lncRNA LINC00477 in polycystic ovary syndrome (PCOS), especially the impacts of LINC00477 on the proliferation and migration of human granulosa cells and the related mechanisms. Methods qRT-PCR analysis was performed to examine the expression pattern of LINC00477 in serum samples of PCOS patients as well as PCOS animal models. The effect of LINC00477 on the viability and apoptosis of ovarian granulosa cells was detected by MTT and flow cytometry assays. The correlation between LINC00477 and miR-128 was verified by bioinformatics analysis and dual-luciferase reporter and RNA pull-down assays. Finally, rescue assays were performed to analyze the effects of the LINC00477-miR-128 axis on the biological behaviors of granulosa cells. Results LINC00477 was significantly upregulated in the serum of PCOS patients as well as PCOS mouse models. LINC00477 overexpression inhibited the proliferation and promoted the apoptosis of granulosa cells, whereas knockdown of LINC00477 yielded the opposite effects. Moreover, miR-128 mimics partially abrogated the effect of LINC00477 on granulosa cells. Conclusion LINC00477 may function as a ceRNA to inhibit proliferation and apoptosis of granulosa cells by modulating miR-128 expression.

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miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

Acta Biochimica Polonica ◽

10.18388/abp.2020_5441 ◽

2021 ◽

Author(s):

Shan Zhou ◽

Liang Xia ◽

Yuanyuan Chen ◽

Weiying Guo ◽

Jinxing Hu

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Polycystic Ovary Syndrome ◽

Cell Viability ◽

Granulosa Cell ◽

Granulosa Cells ◽

Polycystic Ovary ◽

Healthy Controls ◽

Ovarian Dysfunction ◽

Ovary Syndrome

Abnormal proliferation of granulosa cells is implicated in ovarian dysfunction and dysregulated folliculogenesis in the polycystic ovary syndrome (PCOS). Aberrant microRNA (miRNA) expression might contribute to disordered folliculogenesis and granulosa cell proliferation in PCOS. This study aimed to investigate the roles of miR-3188 in ovarian dysfunction, as well as the mechanism involved in granulosa cell proliferation in PCOS. Firstly, peripheral blood samples were isolated from PCOS patients and healthy controls, and qRT-PCR analysis demonstrated a dramatic increase in miR-3188 in PCOS patients when compared to the healthy controls. Secondly, miR-3188 overexpression increased cell viability of the granulosa-like tumor cell line (KGN). However, cell viability of KGN was repressed by interference with miR-3188. MiR-3188 promoted cell cycle of KGN through increasing cyclinD1 and decreasing p21 levels. Moreover, cell apoptosis was suppressed by miR-3188 in KGN, indicated by enhanced Bcl-2, and reduced Bax and cleaved caspase-3 levels, whereas knockdown of miR-3188 resulted in opposite effects. Lastly, potassium voltage-gated channel subfamily A member 5 (KCNA5) was verified as a target of miR-3188. KCNA5 expression was decreased and displayed negative correlation with miR-3188 levels in PCOS patients. Overexpression of KCNA5 attenuated the promotive effects of miR-3188 on cell viability and cell cycle in KGN. In conclusion, miR-3188, a key miRNA enhanced in PCOS, promoted granulosa cell proliferation through down-regulation of KCNA5, providing a new therapeutic target for PCOS.

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Knockdown of circ-FURIN suppresses the proliferation and induces apoptosis of granular cells in polycystic ovary syndrome via miR-195-5p/BCL2 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00891-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yongqian Chen ◽

Jintian Miao ◽

Ge Lou

Keyword(s):

Cell Proliferation ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Luciferase Reporter ◽

Circular Rnas ◽

The Novel ◽

Granular Cells ◽

Ovary Syndrome ◽

Endocrine Disease ◽

Proliferation And Apoptosis

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine disease that increases the risk of infertility. Circular RNAs (circRNAs) play important roles in regulating the biological processes of PCOS. Our study was designed to explore the function of circ-FURIN in PCOS. Methods Circ-FURIN expression was detected using RT-qPCR. The protein expression of AVEN, BCL2, XIAP and AREL1 was measured using western blot. Dual-luciferase reporter and RNA pull-down assays were applied to clarify the interaction between miR-195-5p and circ-FURIN or BCL2. Functionally, cell proliferation was assessed by MTT and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Results Circ-FURIN was upregulated in PCOS patients and granular cells (GCs). Knockdown of circ-FURIN inhibited cell proliferation and promoted apoptosis of KGN cells, along with the increased expression of caspase-3 and Bax and the decreased levels of p-PI3K. Gene ontology (GO) analysis indicated circ-FURIN is associated with apoptotic signaling pathway and cell death. Subsequently, BCL2 expression was elevated in patients with PCOS and positively regulated by circ-FURIN. Furthermore, circ-FURIN was served as a sponge of miR-195-5p to directly target to BCL2. The levels of miR-195-5p were reduced in PCOS and KGN cells. Knockdown of circ-FURIN decreased the expression of BCL2, which was abolished by miR-195-5p inhibitor. At last, rescue experiments revealed that overexpression of BCL2 reversed the effects of circ-FURIN knockdown on cell proliferation and apoptosis of KGN cells. Conclusions Loss of circ-FURIN alleviated the development of PCOS via miR-195-5p/BCL2 axis. Circ-FURIN may be the novel biomarker for PCOS.

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