The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
Linda Nötzold
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Lukas Frank
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Minakshi Gandhi
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Maria Polycarpou-Schwarz
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Matthias Groß
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Manuel Gunkel
(ViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg University)
Nina Beil
(ViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg University)
Holger Erfle
(ViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg University)
Nathalie Harder
(Department of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center (DKFZ))
Karl Rohr
(Department of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center (DKFZ))
Jakob Trendel
(German Cancer Research Center (DKFZ), Excellence Cluster CellNetworks, Heidelberg University)
Jeroen Krijgsveld
(German Cancer Research Center (DKFZ), Excellence Cluster CellNetworks, Heidelberg University)
Thomas Longerich
(Institute of Pathology University Hospital RWTH Aachen)
Peter Schirmacher
(Institute of Pathology, University Hospital Heidelberg)
Michael Boutros
(Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University)
Sylvia Erhardt
(Center for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance and CellNetworks Excellence Cluster, Heidelberg University)
Sven Diederichs
(Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ))
Abstract In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated in cancer entities to analyse their impact on cell division by using time-lapse microscopy. We identified 26 lncRNAs affecting cell morphology and cell cycle including LINC00152. This transcript was ubiquitously expressed in many human cell lines and its RNA levels were significantly upregulated in lung, liver and breast cancer tissues. A comprehensive sequence analysis of LINC00152 revealed a highly similar paralog annotated as MIR4435-2HG and several splice variants of both transcripts. The shortest and most abundant isoform preferentially localized to the cytoplasm. Cells depleted of LINC00152 arrested in prometaphase of mitosis and showed reduced cell viability. In RNA affinity purification (RAP) studies, LINC00152 interacted with a network of proteins that were associated with M phase of the cell cycle. In summary, we provide new insights into the properties and biological function of LINC00152 suggesting that this transcript is crucial for cell cycle progression through mitosis and thus, could act as a non-coding oncogene.
Linda Nötzold, Lukas Frank, Minakshi Gandhi, et al. (2017). "The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells". Scientific Reports. https://doi.org/10.1038/s41598-017-02357-0