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LncRNA LOC102176306 在山羊睾丸发育中发挥重要作用。

LncRNA LOC102176306 plays important roles in goat testicular development.

机构信息

Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

出版信息

Reproduction. 2021 May;161(5):523-537. doi: 10.1530/REP-20-0568.

Abstract

Long ncRNAs regulate a complex array of fundamental biological processes, while its molecular regulatory mechanism in Leydig cells (LCs) remains unclear. In the present study, we established the lncRNA LOC102176306/miR-1197-3p/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) regulatory network by bioinformatic prediction, and investigated its roles in goat LCs. We found that lncRNA LOC102176306 could efficiently bind to miR-1197-3p and regulate PPARGC1A expression in goat LCs. Downregulation of lncRNA LOC102176306 significantly supressed testosterone (T) synthesis and ATP production, decreased the activities of antioxidant enzymes and mitochondrial complex I and complex III, caused the loss of mitochondrial membrane potential, and inhibited the proliferation of goat LCs by decreasing PPARGC1A expression, while these effects could be restored by miR-1197-3p inhibitor treatment. In addition, miR-1197-3p mimics treatment significantly alleviated the positive effects of lncRNA LOC102176306 overexpression on T and ATP production, antioxidant capacity and proliferation of goat LCs. Taken together, lncRNA LOC102176306 functioned as a sponge for miR-1197-3p to maintain PPARGC1A expression, thereby affecting the steroidogenesis, cell proliferation and oxidative stress of goat LCs. These findings extend our understanding of the molecular mechanisms of T synthesis, cell proliferation and oxidative stress of LCs.

摘要

长链非编码 RNA 调节着一系列复杂的基本生物学过程,但其在间质细胞(LCs)中的分子调节机制尚不清楚。在本研究中,我们通过生物信息学预测建立了 lncRNA LOC102176306/miR-1197-3p/过氧化物酶体增殖物激活受体γ共激活因子 1α(PPARGC1A)调控网络,并研究了其在山羊 LCs 中的作用。我们发现 lncRNA LOC102176306 可以有效地与 miR-1197-3p 结合,并调节山羊 LCs 中的 PPARGC1A 表达。下调 lncRNA LOC102176306 显著抑制了睾酮(T)的合成和 ATP 的产生,降低了抗氧化酶和线粒体复合物 I 和复合物 III 的活性,导致线粒体膜电位丧失,并通过降低 PPARGC1A 的表达抑制了山羊 LCs 的增殖,而 miR-1197-3p 抑制剂处理可恢复这些作用。此外,miR-1197-3p 模拟物处理显著缓解了 lncRNA LOC102176306 过表达对 T 和 ATP 产生、抗氧化能力和山羊 LCs 增殖的正向作用。综上所述,lncRNA LOC102176306 作为 miR-1197-3p 的海绵,维持了 PPARGC1A 的表达,从而影响了山羊 LCs 的类固醇生成、细胞增殖和氧化应激。这些发现扩展了我们对 T 合成、LCs 细胞增殖和氧化应激分子机制的理解。

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