Senescence-associated long non-coding RNA (SALNR) delays oncogene-induced senescence through NF90 regulation [RNA]

October 21st, 2015 by Wu, C. L., Wang, Y., Jin, B., Chen, H., Xie, B.-S., Mao, Z.-B.

Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNA has been characterized functionally in aging. In this study, we used human fibroblast cell to investigate genome-wide lncRNA expression during cellular senescence. We identified 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 pre-malignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with nuclear factor of activated T-cells 90 kDa (NF90), a 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 (SA-miRNAs). Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress SA-miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulate cellular senescence at least partly through changing NF90 activity.