We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The Role of APAL/ST8SIA6-AS1 lncRNA in PLK1 Activation and Mitotic Catastrophe of Tumor Cells.
- Authors
Luo, Man-Li; Li, Jingjing; Shen, Liping; Chu, Junjun; Guo, Qiannan; Liang, Guorun; Wu, Wei; Chen, Jianing; Chen, Rufu; Song, Erwei
- Abstract
<bold>Background: </bold>Tumor growth can be addicted to vital oncogenes, but whether long noncoding RNAs (lncRNAs) are essential to cancer survival is largely uncharacterized.<bold>Methods: </bold>We retrieved Gene Expression Omnibus datasets to identify lncRNA overexpression in 257 cancers vs 196 normal tissues and analyzed the association of ST8SIA6-AS1 (termed Aurora A/Polo-like-kinase 1 [PLK1]-associated lncRNA, APAL) with the clinical outcomes of multiple types of cancer from public RNA sequencing and microarray datasets as well as from in-house cancer cohorts. Loss- and gain-of-function experiments were performed to explore the role of APAL in cancers in vitro and in vivo. RNA pulldown and RNA immunoprecipitation were used to investigate APAL-interacting proteins. All statistical tests were two-sided.<bold>Results: </bold>APAL is overexpressed in multiple human cancers associated with poor clinical outcome of patients. APAL knockdown causes mitotic catastrophe and massive apoptosis in human breast, lung, and pancreatic cancer cells. Overexpressing APAL accelerates cancer cell cycle progression, promotes proliferation, and inhibits chemotherapy-induced apoptosis. Mechanism studies show that APAL links up PLK1 and Aurora A to enhance Aurora A-mediated PLK1 phosphorylation. Notably, targeting APAL inhibits the growth of breast and lung cancer xenografts in vivo (MCF-7 xenografts: mean tumor weight, control = 0.18 g [SD = 0.03] vs APAL locked nucleic acids = 0.07 g [SD = 0.02], P < .001, n = 8 mice per group; A549 xenografts: mean tumor weight control = 0.36 g [SD = 0.10] vs APAL locked nucleic acids = 0.10 g [SD = 0.04], P < .001, n = 9 mice per group) and the survival of patient-derived breast cancer organoids in three-dimensional cultures.<bold>Conclusions: </bold>Our data highlight the essential role of lncRNA in cancer cell survival and the potential of APAL as an attractive therapeutic target for a broad-spectrum of cancers.
- Subjects
LUNG cancer; NUCLEIC acids; PANCREATIC intraepithelial neoplasia; NUCLEOTIDE sequence; NON-coding RNA; CELL cycle; SYNCRIP protein; RNA metabolism; PROTEIN metabolism; PROTEINS; RESEARCH; XENOGRAFTS; ANIMAL experimentation; RESEARCH methodology; CELL cycle proteins; RNA; CELL physiology; EVALUATION research; MEDICAL cooperation; COMPARATIVE studies; TRANSFERASES; TUMORS; CELL lines; MICE
- Publication
JNCI: Journal of the National Cancer Institute, 2020, Vol 112, Issue 4, p356
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djz134