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长链非编码RNA-MSTRG.19083.1作为miR-429-y的海绵靶向NTRK2,通过cAMP途径调节牦牛睾丸和隐睾症中的昼夜节律。

LncRNA-MSTRG.19083.1 Targets NTRK2 as a miR-429-y Sponge to Regulate Circadian Rhythm via the cAMP Pathway in Yak Testis and Cryptorchidism.

作者信息

Li Tianan, Yan Qiu, Nan Jinghong, Huang Xue, Wang Ruiqing, Zhang Yong, Zhao Xingxu, Wang Qi

机构信息

College of Veterinary Medicine, Gansu Agriculture University, Lanzhou 730070, China.

Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China.

出版信息

Int J Mol Sci. 2024 Dec 18;25(24):13553. doi: 10.3390/ijms252413553.

Abstract

Long noncoding RNAs (LncRNAs) play essential roles in numerous biological processes in mammals, such as reproductive physiology and endocrinology. Cryptorchidism is a common male reproductive disease. Circadian rhythms are actively expressed in the reproductive system. In this study, a total of 191 LncRNAs were obtained from yak testes and cryptorchids. Then, we identified NTRK2's relationship to circadian rhythm and behavioral processes. Meanwhile, the ceRNA (LncRNA-MSTRG.19083.1/miR-429-y/NTRK2) network was constructed, and its influence on circadian rhythm was revealed. The results showed that NTRK2 and LncRNA-MSTRG.19083.1 were significantly upregulated, and miR-429-y was obviously decreased in cryptorchid tissue; NTRK2 protein was mainly distributed in the Leydig cells of the testis. In addition, the upregulation of the expression level of miR-429-y resulted in the significant downregulation of LncRNA and NTRK2 levels, while the mRNA and protein levels of CREB, CLOCK, and BMAL1 were significantly upregulated; the knockdown of miR-429-y resulted in the opposite changes. Our findings suggested that LncRNA-MSTRG.19083.1 competitively binds to miR-429-y to target NTRK2 to regulate circadian rhythm through the cAMP pathway. Taken together, the results of our study provide a comprehensive understanding of how the LncRNA-miRNA-mRNA networks operate when yak cryptorchidism occurs. Knowledge of circadian-rhythm-associated mRNAs and LncRNAs could be useful for better understanding the relationship between circadian rhythm and reproduction.

摘要

长链非编码RNA(LncRNAs)在哺乳动物的众多生物学过程中发挥着重要作用,如生殖生理学和内分泌学。隐睾症是一种常见的男性生殖疾病。昼夜节律在生殖系统中活跃表达。在本研究中,共从牦牛睾丸和隐睾中获得了191种LncRNAs。然后,我们确定了神经营养酪氨酸激酶受体2(NTRK2)与昼夜节律和行为过程的关系。同时,构建了竞争性内源RNA(ceRNA,即LncRNA-MSTRG.19083.1/miR-429-y/NTRK2)网络,并揭示了其对昼夜节律的影响。结果表明,在隐睾组织中,NTRK2和LncRNA-MSTRG.19083.1显著上调,而miR-429-y明显下调;NTRK2蛋白主要分布在睾丸的间质细胞中。此外,miR-429-y表达水平的上调导致LncRNA和NTRK2水平显著下调,而环磷腺苷效应元件结合蛋白(CREB)、昼夜运动输出周期蛋白1(CLOCK)和脑与肌肉Arnt样蛋白1(BMAL1)的mRNA和蛋白水平显著上调;miR-429-y的敲低则导致相反的变化。我们的研究结果表明,LncRNA-MSTRG.19083.1通过cAMP途径竞争性结合miR-429-y以靶向NTRK2来调节昼夜节律。综上所述,我们的研究结果全面阐述了牦牛隐睾症发生时LncRNA- miRNA-mRNA网络的运作机制。了解与昼夜节律相关的mRNA和LncRNAs可能有助于更好地理解昼夜节律与生殖之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fac9/11678581/88135cff0f55/ijms-25-13553-g001.jpg

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