Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation
Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation
复制标题
衰老相关长非编码 RNA (SALNR) 通过 NF90 调节延迟癌基因诱导的衰老
DOI：
10.1074/jbc.m115.661785
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发表时间：
2015-12-11
影响因子：
4.8
通讯作者：
Mao, Ze-Bin
中科院分区：
文献类型：
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作者：
Wu, Cheng-Lin;Wang, Yu;Mao, Ze-Bin
长链非编码RNA（lncRNA）是近年来发现的一类重要的生物学和病理学调控因子。虽然已经鉴定了许多lncRNA，但很少有lncRNA在衰老中具有功能特征。在这项研究中，我们使用人类成纤维细胞，研究细胞衰老过程中全基因组lncRNA的表达。与年轻细胞相比，Weidentified 968个下调的lncRNA和899个上调的lncRNA。在这些lncRNA中，我们表征了衰老相关lncRNA（SALNR），其表达在细胞衰老期间和癌前结肠腺瘤中减少。SALNR的过表达延缓了成纤维细胞的衰老。此外，我们发现SALNR与NF 90（活化T细胞的核因子，90 kDa）相互作用，NF 90是一种抑制miRNA生物合成的RNA结合蛋白。我们证明NF 90是SALNR下游靶点，其抑制导致过早衰老和衰老相关miRNA的表达增强。此外，我们的数据表明，Ras诱导的应激促进NF 90核仁易位并抑制其抑制衰老相关miRNA生物合成的能力，这可以通过SALNR过表达来挽救。这些数据表明lncRNA SALNR至少部分地通过改变NF 90活性来调节细胞衰老。
Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence. Weidentified 968 down-regulated lncRNAs and 899 up-regulated lncRNAs in senescent cells compared with young cells. Among these lncRNAs, we characterized a senescence-associated lncRNA (SALNR), whose expression was reduced during cellular senescence and in premalignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with NF90 (nuclear factor of activated T-cells, 90 kDa), an RNA-binding protein suppressing miRNA biogenesis. We demonstrated that NF90 is a SALNR downstream target, whose inhibition led to premature senescence and enhanced expressions of senescence-associated miRNAs. Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress senescence-associated miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity.