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Bta-miR-127 通过靶向牛睾丸支持细胞中的 ITGA6 抑制分泌、增殖并促进凋亡。

Bta-miR-127 inhibits secretion, proliferation and promotes apoptosis by targeting ITGA6 in bovine Sertoli cell.

机构信息

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 3):126838. doi: 10.1016/j.ijbiomac.2023.126838. Epub 2023 Sep 13.

Abstract

Sertoli cell (SC) play a critical role in the spermatogenesis process involved in male fecundity and reproductive potential. SC development is regulated by microRNAs (miRNAs). However, the effect and molecular mechanism of miRNAs and target genes on bovine immature SC remains poorly understood. In this study, bta-miR-127 overexpression in SC inhibited cell secretion, proliferation, cell viability, and S-phase cells number. However, inhibition of bta-miR-127 had the opposite effect. An over-expression of bta-miR-127 significantly promotes SC apoptosis, and bta-miR-127 inhibition can significantly inhibit this process. These results reveal that bta-miR-127 is an inhibitor of SC proliferation and secretion. A combination of transcriptome sequencing, bioinformatics analysis, and dual-luciferase reporter assay showed that ITGA6 was targeted by bta-miR-127. The small interfering RNA of ITGA6 (si-ITGA6) inhibits SC proliferation and secretion, as well as promotes apoptosis. The SC proliferation and secretion marker genes, cell viability, and S phase cell number in co-transfected si-ITGA6 + miR-127 inhibitor was significantly lower than those of the bta-miR-127 inhibitor group. These results further confirmed that bta-miR-127 targeting ITGA6 inhibits the SC proliferation and secretion, and promotes SC apoptosis. These findings proposed a novel miRNA (bta-miR-127) that impeded bovine SC proliferation and promoted SC apoptosis through downregulation of ITGA6.

摘要

支持细胞 (SCs) 在雄性生育力和生殖潜能所涉及的精子发生过程中起着至关重要的作用。SCs 的发育受 microRNAs (miRNAs) 调控。然而,miRNAs 和靶基因对牛未成熟SCs 的影响和分子机制仍知之甚少。在这项研究中,SCs 中的 bta-miR-127 过表达抑制了细胞分泌、增殖、细胞活力和 S 期细胞数量。然而,bta-miR-127 的抑制作用则相反。bta-miR-127 的过表达显著促进了 SC 的凋亡,而 bta-miR-127 的抑制可以显著抑制这一过程。这些结果表明 bta-miR-127 是 SC 增殖和分泌的抑制剂。转录组测序、生物信息学分析和双荧光素酶报告基因检测的组合表明,ITGA6 是 bta-miR-127 的靶基因。ITGA6 的小干扰 RNA (si-ITGA6) 抑制了 SC 的增殖和分泌,同时促进了凋亡。共转染 si-ITGA6+miR-127 抑制剂的 SC 增殖和分泌标志物基因、细胞活力和 S 期细胞数量明显低于 bta-miR-127 抑制剂组。这些结果进一步证实了 bta-miR-127 通过靶向 ITGA6 抑制 SC 的增殖和分泌,并促进 SC 的凋亡。这些发现提出了一种新的 miRNA (bta-miR-127),它通过下调 ITGA6 来阻碍牛 SC 的增殖并促进 SC 的凋亡。

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