A novel mitosis-associated lncRNA, MA-linc1, is required for cell cycle progression and sensitizes cancer cells to Paclitaxel

Oncotarget
Or BidaDoron Ginsberg

Abstract

Long noncoding RNAs (lncRNAs) are major regulators of many cellular processes including cell cycle progression and tumorigenesis. In this study, we identify a novel lncRNA, MA-linc1, and reveal its effects on cell cycle progression and cancer growth. Inhibition of MA-linc1 expression alters cell cycle distribution, leading to a decrease in the number of G1 cells and a concomitant increase in all other stages of the cell cycle, and in particular G2/M, suggesting its involvement in the regulation of M phase. Accordingly, knock down of MA-linc1 inhibits M phase exit upon release from a mitotic block. We further demonstrate that MA-linc1 predominantly functions in cis to repress expression of its neighboring gene, Purα, which is often deleted in human cancers and whose ectopic expression inhibits cell cycle progression. Knock down of Purα partially rescues the MA-linc1 dependent inhibition of M phase exit. In agreement with its suggested role in M phase, inhibition of MA-linc1 enhances apoptotic cell death induced by the antimitotic drug, Paclitaxel and this enhancement of apoptosis is rescued by Purα knockdown. Furthermore, high levels of MA-linc1 are associated with reduced survival in human breast and lung cancer patients.Taken ...Continue Reading

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Citations

Feb 17, 2017·Biochemical Society Transactions·Aldema Sas-ChenYosef Yarden
Jan 20, 2017·BioMed Research International·Liang GuoGuozheng Xu
Apr 21, 2017·Oncotarget·Lital Gasri-PlotnitskyDoron Ginsberg
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Mar 10, 2021·Trends in Genetics : TIG·Giulia Guiducci, Lovorka Stojic

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Methods Mentioned

BETA
RNA
ChIP
transfection
fluorescence-activated cell sorting
FACS
PCR
electrophoresis
immunoprecipitation
flow-cytometry
RNA-seq

Software Mentioned

TCGA
Ensembl
RSEM
Bioconductor
DESeq
FeatureCounts

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