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长链非编码 RNA MALAT1 通过调控 miR-205/CREB1 轴调控小鼠颗粒细胞凋亡和 17β-雌二醇合成。

lncRNA MALAT1 Regulates Mouse Granulosa Cell Apoptosis and 17-Estradiol Synthesis via Regulating miR-205/CREB1 Axis.

机构信息

Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.

Institute of Animal Biotechnology, Jilin Academy of Agricultural Sciences, Changchan 130033, China.

出版信息

Biomed Res Int. 2021 Feb 17;2021:6671814. doi: 10.1155/2021/6671814. eCollection 2021.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a known long noncoding RNA, was reported to play a crucial role in follicular growth and ovarian disease. However, the physiological function of MALAT1 in mouse granulosa cells (mGCs) remains largely unclear. The aims of this study were to determine the biological function and molecular mechanism of MALAT1 in mGCs. We knocked down MALAT1 in mGCs by using siRNA against MALAT1. We found that knockdown of MALAT1 promoted apoptosis and caspase-3/9 activities in mGCs. Enzyme-linked immunosorbent assay demonstrated that knockdown of MALAT1 significantly decreased the production of estradiol (E2) and progesterone (P4) in mGCs. Mechanistically, MALAT1 serves as a competing endogenous RNA (ceRNA) to sponge microRNA-205 (miR-205), thereby facilitating its downstream target of cyclic AMP response element- (CRE-) binding protein 1 (CREB1). Furthermore, CREB1 overexpression or miR-205 downregulation partially recovered the effect of MALAT1 depletion in mGCs. In summary, these findings suggested that MALAT1 regulated apoptosis and estradiol synthesis of mGCs through the miR-205/CREB1 axis.

摘要

转移相关肺腺癌转录本 1(MALAT1)是一种已知的长非编码 RNA,据报道其在卵泡生长和卵巢疾病中发挥关键作用。然而,MALAT1 在小鼠颗粒细胞(mGC)中的生理功能在很大程度上仍不清楚。本研究旨在确定 MALAT1 在 mGC 中的生物学功能和分子机制。我们使用针对 MALAT1 的 siRNA 敲低 mGC 中的 MALAT1。我们发现,敲低 MALAT1 可促进 mGC 中的细胞凋亡和半胱天冬酶-3/9 活性。酶联免疫吸附试验表明,敲低 MALAT1 可显著降低 mGC 中雌二醇(E2)和孕酮(P4)的产生。机制上,MALAT1 作为竞争性内源 RNA(ceRNA)与 microRNA-205(miR-205)结合,从而促进其下游环磷酸腺苷反应元件结合蛋白 1(CREB1)的靶标。此外,CREB1 过表达或 miR-205 下调部分恢复了 MALAT1 耗竭对 mGC 的影响。总之,这些发现表明 MALAT1 通过 miR-205/CREB1 轴调节 mGC 的细胞凋亡和雌二醇合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c6/7904346/17723d3555d9/BMRI2021-6671814.001.jpg

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