Transcription Factor YY1 Adversely Governs Ovarian Granulosa Cell Growth in PCOS by Transcription Activation-mediated CDKN1C Upregulation

Overview

Journal Funct Integr Genomics

Publisher Springer

Specialties Genetics
Molecular Biology

Date 2024 Sep 24

PMID 39317806

Authors

Shitao Dong

Youbin Liu

Zhimin Yang

Affiliations

Soon will be listed here.

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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