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植物源miR166a - 3p包装到外泌体中,通过靶向APLNR基因进行跨界抑制乳腺细胞增殖并促进细胞凋亡。

Plant-derived miR166a-3p packaged into exosomes to cross-kingdom inhibit mammary cell proliferation and promote apoptosis by targeting APLNR gene.

作者信息

Shi Yiru, Wei Junjie, Nie Ying, Luo Junyi, Chen Ting, Xi Qianyun, Zhang Yongliang, Sun Jiajie

机构信息

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.

出版信息

Int J Biol Macromol. 2025 Jan;286:138470. doi: 10.1016/j.ijbiomac.2024.138470. Epub 2024 Dec 5.

DOI:10.1016/j.ijbiomac.2024.138470
PMID:39645121
Abstract

Plant-derived microRNAs (miRNAs) have attracted significant attention for their potential in cross-kingdom gene regulation, but the mechanisms of their entry, stability, and function in animal bodies need further investigation. We provided an in-depth analysis of tissue-specific miRNA expression in dairy cows, identifying 347 miRNAs, including 16 novel candidates, across 21 normal tissues. Our findings revealed that specific miRNAs, such as miR-192, miR-143, miR-148a, miR-486, and miR-21-5p, showed distinct tissue enrichment. In addition, a total of 167 maize-derived miRNAs were identified in dairy cow tissues, particularly in the rumen, mammary glands, serum, and exosomes. These exogenous miRNAs, which are abundant and conserved among plants, may be absorbed by the SLC46A2 transporter in the rumen epithelium during feeding and distributed to other tissues via exosomal encapsulation. The maize-derived miR166a-3p was highly abundant. Transfection experiments confirmed that miR166a-3p reduces the expression of proliferation markers (PCNA, Cyclin D, and Cyclin E) and the anti-apoptotic gene Bcl2, while upregulating the pro-apoptotic gene Bax. Moreover, exosomes derived from bovine serum were found to mediate these effects, as miR166a-3p-enriched exosomes inhibited cell proliferation and promoted apoptosis, further supporting the cross-kingdom role of plant-derived miRNAs in regulating biological processes. This study enhances the understanding of miRNA regulatory mechanisms, particularly the absorption and systemic transport of plant-derived miRNAs in dairy cows. The findings underscore the potential for using exogenous miRNAs, like miR166a-3p, in agricultural and medical contexts, warranting further investigation into their functions and cross-species interactions.

摘要

植物源微小RNA(miRNA)因其在跨界基因调控中的潜力而备受关注,但其进入动物体内的机制、稳定性及其在动物体内的功能仍需进一步研究。我们深入分析了奶牛组织特异性miRNA表达情况,在21种正常组织中鉴定出347种miRNA,其中包括16种新的候选miRNA。我们的研究结果表明,特定的miRNA,如miR-192、miR-143、miR-148a、miR-486和miR-21-5p,呈现出明显的组织富集现象。此外,在奶牛组织中总共鉴定出167种玉米源miRNA,尤其是在瘤胃、乳腺、血清和外泌体中。这些在植物中丰富且保守的外源miRNA,可能在进食过程中被瘤胃上皮中的SLC46A2转运蛋白吸收,并通过外泌体包裹分布到其他组织。玉米源miR166a-3p含量极高。转染实验证实,miR166a-3p可降低增殖标志物(PCNA、细胞周期蛋白D和细胞周期蛋白E)以及抗凋亡基因Bcl2的表达,同时上调促凋亡基因Bax的表达。此外,发现源自牛血清的外泌体介导了这些作用,因为富含miR166a-3p的外泌体抑制细胞增殖并促进细胞凋亡,进一步支持了植物源miRNA在调节生物学过程中的跨界作用。本研究增进了对miRNA调控机制的理解,特别是植物源miRNA在奶牛体内的吸收和全身运输。研究结果强调了在农业和医学领域使用外源miRNA(如miR166a-3p)的潜力,值得进一步研究其功能和跨物种相互作用。

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