A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation.

Abstract

The transcription factor E2F1 induces both proliferation and apoptosis and is a critical downstream target of the tumor suppressor RB.Long non-coding RNAs (lncRNAs) are major regulators of many cellular processes, including cell cycle progression and cell proliferation. However, the mode of action as well as the transcriptional regulation of most lncRNAs are only beginning to be understood.Here, we report that a novel human lncRNA, LAPAS1, is an E2F1- regulated lncRNA that affects S phase progression. Inhibition of LAPAS1 expression increases percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase. In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.Our data demonstrate that LAPAS1 predominantly functions in trans to repress expression of Sphingolipid Transporter 2 (SPNS2). Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation.Notably, low levels of LAPAS1 are associated with increased survival of kidney cancer patients.Summarily, we identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.