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

Esther Baruch, Tali Nizri-Megnaji, Oron Berkowitz, Doron Ginsberg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1072-1082
Number of pages11
JournalOncotarget
Volume12
Issue number11
DOIs
StatePublished - 25 May 2021

Bibliographical note

Publisher Copyright:
© 2021 Baruch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

We thank Dr. Orly Yaron and Dr. Sarit Lampert for RNA Seq. analysis and Dr. Ilana Lebenthal-Loinger for computational analysis. This work was supported by grants from the Israel Cancer Research Association (ICRF to D.G.) and the Israel Cancer Association (ICA to D.G.).

FundersFunder number
Israel Cancer Research Association
Israel Cancer Research Fund
International Communication Association
Israel Cancer Association

    Keywords

    • Cell cycle
    • Cell proliferation
    • E2F
    • LncRNA

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