A novel E2F1-regulated lncRNA, XLOC_000190, is required for S phase progression and cell proliferation.

Long non-coding RNAs (lncRNAs) are major regulators of many cellular processes including cell cycle progression and cell proliferation. Also, many lncRNAs are frequently aberrantly expressed in various human cancers, with potential roles in both oncogenic and tumor suppressive pathways. The pivotal transcription factor E2F1 induces both proliferation and cell death and is a critical downstream target of the tumor suppressor RB.

Here, we report that the human lncRNA XLOC_000190 is an E2F1- regulated lncRNA that plays a role in S phase progression. XLOC_000190 levels are elevated upon activation of E2F1 and knockdown of E2F1 reduces XLOC_000190 levels. Moreover, expression of XLOC_000190 is cell cycle regulated and peaks near G1/S transition and in early S. Inhibition of XLOC_000190 expression increases percentage of S phase cells, suggesting that XLOC_000190 plays a role in S phase progression. Also, silencing of XLOC_000190 in cells that are synchronized at the G1/S boundary delays progression of cells through S phase. In agreement with its suggested role in S phase, prolonged silencing of XLOC_000190 inhibits proliferation of human cancer cells. Moreover, XLOC_000190 silencing leads to a significant increase in the levels of Sphingolipid Transporter 2 (SPNS2). Importantly, knockdown of SPNS2 rescued the effect of XLOC_000190 silencing on S phase progression. Notably, low levels of XLOC_000190 are associated with increased survival of kidney cancer patients.

In conclusions, our data identify XLOC_000190 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.