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

Zhou, Shouli; Liang, Xiaofeng; Chen, Yuanyuan; Guo, Weiying; Hu, Jinxing

doi:10.18388/abp.2020_5441

Cited by 8 publications

(11 citation statements)

References 22 publications

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“…Consistent with previously published studies [10,11], our data indicates that KCNA5 is downregulated in PCOS. Additionally, compared to the controls, Hsc70 overexpression decreased KCNA5 levels, and Hsc70 knockdown increased KCNA5 expression.…”

Section: Discussionsupporting

confidence: 93%

“…Importantly, Hsc70 interacts with CHIP to facilitate KCNA5 degradation in mammalian cells [8]. KCNA5 is downregulated in PCOS, and KCNA5 upregulation inhibits granulosa cell proliferation in PCOS [10,11]. However, the interplay between Hsc70 and KCNA5 in PCOS has not been reported to date.…”

Section: Discussionmentioning

confidence: 99%

“…KCNA5 is implicated in the proliferation and apoptosis of various cells, such as human mammary epithelial cells and cancer cells [9]. Moreover, KCNA5 is downregulated in PCOS, and KCNA5 overexpression suppresses granulosa cell proliferation in PCOS [10,11]. However, the interaction of Hsc70 with KCNA5 in PCOS has yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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Hsc70 interacts with KCNA5 to promote the proliferation of granulosa cells in polycystic ovarian syndrome

Deng¹,

Wang²

2022

Trop. J. Pharm Res

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Purpose: To investigate the function and interaction of heat-shock cognate protein 70 (Hsc70) and potassium voltage-gated channel subfamily A member 5 (KCNA5) in polycystic ovary syndrome (PCOS).Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were used to measure Hsc70 and KCNA5 expression in PCOS. The effect of Hsc70 on granulosa cell apoptosis was determined by flow cytometry. Cell counting kit-8 (CCK-8) and colony formation assay were used to assess the impact of Hsc70 on cell proliferation, while the interaction of Hsc70 with KCNA5 were evaluated by Western blot, CCK-8, and colony formation assay, respectively.Results: Hsc70 expression was upregulated in PCOS compared to the control (p < 0.05). In granulosa cells, Hsc70 overexpression promoted cell proliferation but inhibited apoptosis (p < 0.05), whereas Hsc70 knockdown suppressed cell proliferation and promoted apoptosis (p < 0.05). Furthermore, KCNA5 expression was downregulated in PCOS (p < 0.05) and was negatively correlated with Hsc70 expression. KCNA5 knockdown promoted granulosa cell proliferation and also attenuated the Hsc70 knockdown-mediated inhibition of granulosa cell proliferation (p < 0.05).Conclusion: Hsc70 promotes granulosa cell proliferation by interacting with KCNA5, further defining the molecular mechanism behind PCOS.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Hsc70 interacts with KCNA5 to promote the proliferation of granulosa cells in polycystic ovarian syndrome

Deng¹,

Wang²

2022

Trop. J. Pharm Res

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“…Liu C et al reported that p53 deacetylation is a crucial step of miR-874-3p induce GCs apoptosis [ 12 ]. miR-3188 promoted the cell cycle by decreasing p21 in KGN cells [ 52 ]. And also, cellular stresses are activated in response to p53 signaling through HB-EGF induction [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

microRNA-194 is increased in polycystic ovary syndrome granulosa cell and induce KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor

Lin

et al. 2021

Reprod Biol Endocrinol

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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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“…miRNAs regulate the function of GCs by altering the expression levels of target genes. For example, in the granulosa-like tumor cell line, miR-1388 promotes cell cycle progression by increasing cyclin D1 and decreasing p21 levels by targeting potassium voltage-gated channel subfamily A member 5 ( KCNA5 ) [ 31 ]. Another study showed that miR-29c participates in the regulation of follicular atresia by inhibiting GC apoptosis by targeting SMARCA2 via the NORFA-SMAD4 axis [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of RBP4 on microRNA Expression Profiles in Porcine Granulosa Cells

Zhao

Rao

Qiu

et al. 2021

Animals

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Retinol binding protein 4 (RBP4) is a transporter of vitamin A that is secreted mainly by hepatocytes and adipocytes. It affects diverse pathophysiological processes, such as obesity, insulin resistance, and cardiovascular diseases. MicroRNAs (miRNAs) have been reported to play indispensable roles in regulating various developmental processes via the post-transcriptional repression of target genes in mammals. However, the functional link between RBP4 and changes in miRNA expression in porcine granulosa cells (GCs) remains to be investigated. To examine how increased expression of RBP4 affects miRNA expression, porcine GCs were infected with RBP4-targeted lentivirus for 72 h, and whole-genome miRNA profiling (miRNA sequencing) was performed. The sequencing data were validated using real-time quantitative polymerase chain reaction (RT-qPCR) analysis. As a result, we obtained 2783 known and 776 novel miRNAs. In the experimental group, 10 and seven miRNAs were significantly downregulated and upregulated, respectively, compared with the control group. Ontology analysis of the biological processes of these miRNAs indicated their involvement in a variety of biological functions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these miRNAs were involved mainly in the chemokine signaling pathway, peroxisome proliferators-activated receptors (PPAR) signaling pathway, insulin resistance pathway, nuclear factor-kappa B(NF-kappa B) signaling pathway, and steroid hormone biosynthesis. Our results indicate that RBP4 can regulate the expression of miRNAs in porcine GCs, with consequent physiological effects. In summary, this study profiling miRNA expression in RBP4-overexpressing porcine GCs provides an important reference point for future studies on the regulatory roles of miRNAs in the porcine reproductive system.

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

Cited by 8 publications

References 22 publications

Hsc70 interacts with KCNA5 to promote the proliferation of granulosa cells in polycystic ovarian syndrome

Hsc70 interacts with KCNA5 to promote the proliferation of granulosa cells in polycystic ovarian syndrome

microRNA-194 is increased in polycystic ovary syndrome granulosa cell and induce KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor

The Effect of RBP4 on microRNA Expression Profiles in Porcine Granulosa Cells

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