Transcription factor YY1 adversely governs ovarian granulosa cell growth in PCOS by transcription activation-mediated CDKN1C upregulation

IF 3.9 4区生物学 Q1 GENETICS & HEREDITY Functional & Integrative Genomics Pub Date : 2024-09-25 DOI:10.1007/s10142-024-01448-2

Shitao Dong, Youbin Liu, Zhimin Yang

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Abstract

Background

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women of childbearing age, making it imperative to explore more biomarkers for PCOS. Furthermore, previous studies have reported that cyclin dependent kinase inhibitor 1 C (CDKN1C) might be associated with PCOS progression. However, the molecular mechanism of CDKN1C involved in PCOS is poorly defined.

Methods

CDKN1C and Yin-Yang-1 (YY1) expression levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. Cell viability, proliferation, cell cycle progression, and cell apoptosis were analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), and flow cytometry assays. Caspase 3 activity was examined using a commercial kit. Binding between YY1 and CDKN1C promoter was predicted by JASPAR and verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays.

Results

CDKN1C and YY1 were highly expressed in PCOS granulosa cells (GCs). Furthermore, CDKN1C silencing could promote cell proliferation and cell cycle process and repress cell apoptosis in human ovarian granulosa cell line KGN cells. For mechanistic analysis, YY1 is directly bound to the promoter of CDKN1C and transcriptional-regulated CDKN1C expression.

Conclusion

YY1-activated CDKN1C might block KGN cell proliferation and induce cell apoptosis, providing a possible therapeutic target for PCOS treatment.

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转录因子 YY1 通过转录激活介导的 CDKN1C 上调，对多囊卵巢综合征的卵巢颗粒细胞生长产生不利影响。

背景：多囊卵巢综合征（PCOS）是育龄妇女常见的内分泌和代谢疾病，因此探索更多的多囊卵巢综合征生物标志物势在必行。此外，之前有研究报告称，细胞周期蛋白依赖性激酶抑制剂 1 C（CDKN1C）可能与多囊卵巢综合征的进展有关。然而，CDKN1C参与多囊卵巢综合症的分子机制尚未明确：方法：采用实时定量聚合酶链式反应（RT-qPCR）和 Western 印迹法测定 CDKN1C 和阴阳-1（YY1）的表达水平。使用 3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2-H-溴化四氮唑（MTT）、5-乙炔基-2'-脱氧尿苷（EdU）和流式细胞仪分析细胞活力、增殖、细胞周期进展和细胞凋亡。使用商业试剂盒检测 Caspase 3 的活性。通过 JASPAR 预测了 YY1 与 CDKN1C 启动子之间的结合，并使用染色质免疫沉淀（ChIP）和双荧光素酶报告实验进行了验证：结果：CDKN1C和YY1在多囊卵巢综合征颗粒细胞（GCs）中高表达。此外，在人卵巢颗粒细胞系 KGN 细胞中，CDKN1C 沉默可促进细胞增殖和细胞周期进程，抑制细胞凋亡。在机理分析方面，YY1直接与CDKN1C的启动子结合并转录调控CDKN1C的表达：结论：YY1激活CDKN1C可能会阻止KGN细胞增殖并诱导细胞凋亡，为治疗多囊卵巢综合征提供了一个可能的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Functional & Integrative Genomics 生物-遗传学

CiteScore

3.50

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?