Human satellite III long noncoding RNA imparts survival benefits to cancer cells

Abstract

Long noncoding RNAs (lncRNAs) are heterogeneous group of transcripts that lack coding potential and have essential roles in gene regulations. Recent days have seen an increasing association of noncoding RNAs with human diseases, especially cancers. One interesting group of noncoding RNAs strongly linked to cancers are heterochromatic repetitive Satellite RNAs. Satellite RNAs are transcribed from pericentromeric heterochromatic region of the human chromosomes. Satellite II RNA, most extensively studied, is upregulated in wide variety of epithelial cancer. Similarly, alpha satellite is over expressed in BRCA1-deficient tumors. Though much is known about alpha satellites and SatII repeats, little is known about Satellite III (SatIII) lncRNAs in human cancers. SatIII repeats, though transcriptionally silent in normal conditions is actively transcribed under condition of stress, mainly heat shock. In this study, we show that colon and breast cancer cells aberrantly transcribes SatIII, in a heat shock factor I (HSF1)-independent manner. Our study also reveals that, the overexpression of SatIII RNA favors cancer cell survival by overriding chemo drug-induced cell death. Interestingly, knockdown of SatIII sensitizes cells toward chemotherapeutic drugs. This sensitization is possibly mediated by restoration of p53 protein expression that facilitates cell death. Heat shock however helps SatIII to continue with its pro-cell survival function. Our results, therefore suggest SatIII to be an important regulator of human cancers. Induction of SatIII is not only a response to the oncogenic stress but also facilitates cancer progression by a distinct pathway that is different from heat stress pathway.