转录因子 c-fos 通过调节 MALAT1/miR-22-3p/STAT1 网络诱导卵巢早衰的发生。
Transcription factor c-fos induces the development of premature ovarian insufficiency by regulating MALAT1/miR-22-3p/STAT1 network.
机构信息
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Avenue, Tianhe District, Guangzhou, Guangdong Province, 510630, P.R. China.
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, No. 9, Jinsui Road, Guangzhou, Guangdong Province, 510623, P.R. China.
出版信息
J Ovarian Res. 2023 Jul 21;16(1):144. doi: 10.1186/s13048-023-01212-3.
BACKGROUND
The current study attempted to investigate the role of transcription factor c-fos in the development of premature ovarian insufficiency (POI) as well as the underlying mechanism involving the MALAT1/miR-22-3p/STAT1 ceRNA network.
METHODS
Bioinformatics analysis was performed to extract POI-related microarray dataset for identifying the target genes. Interaction among c-fos, MALAT1, miR-22-3p, and STAT1 was analyzed. An in vivo POI mouse model was prepared followed by injection of sh-c-fos and sh-STAT1 lentiviruses. Besides, an in vitro POI cell model was constructed to study the regulatory roles of c-fos, MALAT1, miR-22-3p, and STAT1.
RESULTS
c-fos, MALAT1, and STAT1 were highly expressed in ovarian tissues from POI mice and CTX-induced KGN cells, while miR-22-3p was poorly expressed. c-fos targeted MALAT1 and promoted MALAT1 transcription. MALAT1 competitively bound to miR-22-3p and miR-22-3p could suppress STAT1 expression. Mechanically, c-fos aggravated ovarian function impairment in POI mice and inhibited KGN cell proliferation through regulation of the MALAT1/miR-22-3p/STAT1 regulatory network.
CONCLUSION
Our findings highlighted inducing role of the transcription factor c-fos in POI through modulation of the MALAT1/miR-22-3p/STAT1 ceRNA network.
背景
本研究旨在探讨转录因子 c-fos 在卵巢早衰（POI）发展中的作用及其涉及 MALAT1/miR-22-3p/STAT1 ceRNA 网络的潜在机制。
方法
通过生物信息学分析提取与 POI 相关的微阵列数据集，以鉴定靶基因。分析 c-fos、MALAT1、miR-22-3p 和 STAT1 之间的相互作用。制备 POI 小鼠模型，并注射 sh-c-fos 和 sh-STAT1 慢病毒。此外，构建体外 POI 细胞模型，以研究 c-fos、MALAT1、miR-22-3p 和 STAT1 的调节作用。
结果
c-fos、MALAT1 和 STAT1 在 POI 小鼠和 CTX 诱导的 KGN 细胞的卵巢组织中高表达，而 miR-22-3p 低表达。c-fos 靶向 MALAT1 并促进 MALAT1 转录。MALAT1 竞争性结合 miR-22-3p，miR-22-3p 可抑制 STAT1 表达。机制上，c-fos 通过调节 MALAT1/miR-22-3p/STAT1 调控网络加重 POI 小鼠的卵巢功能损伤，抑制 KGN 细胞增殖。
结论
我们的研究结果强调了转录因子 c-fos 通过调节 MALAT1/miR-22-3p/STAT1 ceRNA 网络在 POI 中的诱导作用。
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