周期蛋白 D1 促进致癌免疫 miRNA 和 piRNA 的分泌。
Cyclin D1 promotes secretion of pro-oncogenic immuno-miRNAs and piRNAs.
机构信息
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Wenzhou Medical University, Wenzhou City, Zhejiang, China.
出版信息
Clin Sci (Lond). 2020 Apr 17;134(7):791-805. doi: 10.1042/CS20191318.
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.
调控非编码基因组分泌的分子机制尚未完全阐明。本文研究表明，细胞周期蛋白依赖性激酶的调节亚基 cyclin D1 可调控人类乳腺癌中非编码 RNA 亚型（miRNA、rRNA、tRNA、CDBox、scRNA、HAcaBox、sncRNA、piRNA）的分泌和相对比例。cyclin D1 诱导与肿瘤免疫反应和致癌 miRNA 相关的 miRNA 分泌。miR-21 和 miR-93 与 Toll 样受体 8 结合，触发促转移炎症反应，占 cyclin D1 诱导分泌 miRNA 转录本的>85%。此外，cyclin D1 还调控 P 元素诱导 Wimpy 测试基因（PIWI）相互作用 RNA（piRNA）的分泌，包括调控干细胞扩增的 piR-016658 和 piR-016975，增加 Argonaute 家族 PIWI 成员 piwil2 在 ERα阳性乳腺癌中的丰度。cyclin D1 介导的促肿瘤发生的免疫 miRNA 和 piRNA 的分泌可能有助于肿瘤的发生和发展。
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