Cyclin D1 promotes secretion of pro-oncogenic immuno-miRNAs and piRNAs.

Clinical Science (London, England : 1979) Pub Date : 2020-04-17 DOI:10.1042/CS20191318

Jinhui Lü, Qian Zhao, Xin Ding, Yuefan Guo, Yuan Li, Zhen Xu, Shujun Li, Zhongrui Wang, Lei Shen, Huang-Wen Chen, Zuoren Yu, Richard G Pestell

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引用次数: 12

Abstract

The molecular mechanisms governing the secretion of the non-coding genome are poorly understood. We show herein that cyclin D1, the regulatory subunit of the cyclin-dependent kinase that drives cell-cycle progression, governs the secretion and relative proportion of secreted non-coding RNA subtypes (miRNA, rRNA, tRNA, CDBox, scRNA, HAcaBox. scaRNA, piRNA) in human breast cancer. Cyclin D1 induced the secretion of miRNA governing the tumor immune response and oncogenic miRNAs. miR-21 and miR-93, which bind Toll-Like Receptor 8 to trigger a pro-metastatic inflammatory response, represented >85% of the cyclin D1-induced secreted miRNA transcripts. Furthermore, cyclin D1 regulated secretion of the P-element Induced WImpy testis (PIWI)-interacting RNAs (piRNAs) including piR-016658 and piR-016975 that governed stem cell expansion, and increased the abundance of the PIWI member of the Argonaute family, piwil2 in ERα positive breast cancer. The cyclin D1-mediated secretion of pro-tumorigenic immuno-miRs and piRNAs may contribute to tumor initiation and progression.

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Cyclin D1促进促癌免疫mirna和pirna的分泌。

调控非编码基因组分泌的分子机制尚不清楚。我们在此表明，cyclin D1是驱动细胞周期进程的周期蛋白依赖性激酶的调控亚基，它控制着分泌的非编码RNA亚型(miRNA、rRNA、tRNA、CDBox、scRNA、HAcaBox)的分泌和相对比例。scaRNA, piRNA)在人类乳腺癌中的作用。Cyclin D1诱导调控肿瘤免疫应答和致癌miRNA的分泌。miR-21和miR-93结合toll样受体8触发促转移性炎症反应，占细胞周期蛋白d1诱导的分泌miRNA转录物的85%以上。此外，cyclin D1调节p元素诱导的WImpy睾丸(PIWI)相互作用rna (piRNAs)的分泌，包括控制干细胞扩增的piR-016658和piR-016975，并增加ERα阳性乳腺癌中Argonaute家族PIWI成员piwil2的丰度。细胞周期蛋白d1介导的促肿瘤免疫mirs和pirna的分泌可能有助于肿瘤的发生和发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Clinical Science (London, England : 1979)

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