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LncRNA SNHG12 通过海绵吸附 miR-129 和 miR-125b 促进多囊卵巢综合征颗粒细胞增殖并抑制细胞凋亡。

LncRNA SNHG12 promotes cell proliferation and inhibits apoptosis of granulosa cells in polycystic ovarian syndrome by sponging miR-129 and miR-125b.

机构信息

Department of Obstetrics and Gynecology, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, China.

Department of Gynecology, Jiaojiang Maternal and Child Health Hospital, Taizhou, Zhejiang, 318000, China.

出版信息

J Ovarian Res. 2024 Apr 2;17(1):72. doi: 10.1186/s13048-024-01392-6.

DOI:10.1186/s13048-024-01392-6
PMID:38566229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10986130/
Abstract

BACKGROUND

Polycystic ovarian syndrome (PCOS) is the most common endocrine disease in women of childbearing age which is often associated with abnormal proliferation or apoptosis of granulosa cells (GCs). Studies proved that long non-coding RNA SNHG12 (lncRNA SNHG12) is significantly increased in ovarian cancer and cervical cancer patients and cells. The inhibition of lncRNA SNHG12 restrains the proliferation, migration, and invasion in tumor cells.

OBJECTIVE

This study explores the role of lncRNA SNHG12 in the apoptosis of GCs in PCOS and the underlying regulated mechanism.

METHODS

In this study, the injection of dehydroepiandrosterone (DHEA) successfully induced the PCOS model in SD rats. The human granulosa-like tumor cell line KGN was incubated with insulin to assess the effects of lncRNA SNHG12 on GC proliferation and apoptosis.

RESULTS

Overexpression of lncRNA SNHG12 influenced the body weight, ovary weight, gonadal hormone, and pathological changes, restrained the expressions of microRNA (miR)-129 and miR-125b, while downregulation of lncRNA SNHG12 exerted the opposite effects in PCOS rats. After silencing lncRNA SNHG12 in cells, the cell viability and proliferation were lessened whereas apoptosis of cells was increased. A loss-of-functions test was implemented by co-transfecting miR-129 and miR-125b inhibitors into lncRNA SNHG12-knocking down cells to analyze the effects on cell viability and apoptosis. Next, the existence of binding sites of SNHG12 and miR-129/miR-125b was proved based on the pull-down assay.

CONCLUSION

lncRNA SNHG12 might be a potential regulatory factor for the development of PCOS by sponging miR-129 and miR-125b in GCs.

摘要

背景

多囊卵巢综合征(PCOS)是育龄妇女最常见的内分泌疾病,常伴有颗粒细胞(GCs)异常增殖或凋亡。研究证实,长链非编码 RNA SNHG12(lncRNA SNHG12)在卵巢癌和宫颈癌患者及细胞中显著增加。抑制 lncRNA SNHG12 可抑制肿瘤细胞的增殖、迁移和侵袭。

目的

本研究探讨 lncRNA SNHG12 在 PCOS 中 GC 凋亡中的作用及其潜在调节机制。

方法

本研究通过注射脱氢表雄酮(DHEA)成功诱导 SD 大鼠 PCOS 模型。用胰岛素孵育人颗粒细胞样肿瘤细胞系 KGN,评估 lncRNA SNHG12 对 GC 增殖和凋亡的影响。

结果

lncRNA SNHG12 的过表达影响 PCOS 大鼠的体重、卵巢重量、性腺激素和病理变化,抑制 microRNA(miR)-129 和 miR-125b 的表达,而下调 lncRNA SNHG12 则产生相反的作用。沉默细胞中的 lncRNA SNHG12 后,细胞活力和增殖减少,而细胞凋亡增加。通过共转染 miR-129 和 miR-125b 抑制剂到 lncRNA SNHG12 敲低细胞中进行功能丧失试验,分析对细胞活力和凋亡的影响。接下来,通过下拉实验证明了 SNHG12 与 miR-129/miR-125b 之间存在结合位点。

结论

lncRNA SNHG12 可能通过在 GCs 中海绵吸附 miR-129 和 miR-125b 成为 PCOS 发展的潜在调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/a2fb5af5b573/13048_2024_1392_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/5e6785afa3f1/13048_2024_1392_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/883be75608e0/13048_2024_1392_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/1297791a3c71/13048_2024_1392_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/7cbd264f370d/13048_2024_1392_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/7c84844866f0/13048_2024_1392_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/a2fb5af5b573/13048_2024_1392_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/5e6785afa3f1/13048_2024_1392_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/883be75608e0/13048_2024_1392_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/1297791a3c71/13048_2024_1392_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/7cbd264f370d/13048_2024_1392_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/7c84844866f0/13048_2024_1392_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/10986130/a2fb5af5b573/13048_2024_1392_Fig6_HTML.jpg

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