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Published VersionCC BY V4.0, Open Access
Journal article
The long non-coding RNA GHSROS reprograms prostate cancer cell lines towards a more aggressive phenotype
PeerJ, Vol.9, pp.1-29
2021
Appears in Cancer Research Cluster Research Collection
Abstract
It is now appreciated that long non-coding RNAs (lncRNAs) are important players in orchestrating cancer progression. In this study we characterized GHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Transcriptome data revealed that GHSROS alters the expression of cancer-associated genes. Functional analyses in vitro showed that GHSROS mediates tumor growth, migration and survival, and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation of GHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell lines in vitro was recapitulated in a subcutaneous xenograft model. Conversely, in vitro antisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably, GHSROS modulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest that GHSROS can reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.
Details
- Title
- The long non-coding RNA GHSROS reprograms prostate cancer cell lines towards a more aggressive phenotype
- Authors
- Patrick B Thomas - Queensland University of TechnologyPenny L Jeffery - Queensland University of TechnologyManuel Gahete - Instituto Maimónides de Investigación Biomédica de CórdobaEliza J Whiteside - University of Southern QueenslandCarina M Walpole - Queensland University of TechnologyMichelle Maugham-Macan - Queensland University of TechnologyLidija Jovanovic - Queensland University of TechnologyJennifer H Gunter - Queensland University of TechnologyElizabeth D Williams - Queensland University of TechnologyColleen C Nelson - Queensland University of TechnologyAdrian C Herington - Queensland University of TechnologyRaul M. Luque - Instituto Maimónides de Investigación Biomédica de CórdobaRakesh Veedu - Murdoch UniversityLisa K Chopin - Queensland University of TechnologyInge Seim - Queensland University of Technology
- Publication details
- PeerJ, Vol.9, pp.1-29
- Publisher
- PeerJ, Ltd.
- Date published
- 2021
- DOI
- 10.7717/peerj.10280
- ISSN
- 2167-8359; 2167-8359
- Copyright note
- Copyright 2021 Thomas et al. Distributed under Creative Commons CC-BY 4.0
- Data Availability
- The data are available at NCBI GEO: GSE86097, GSE103320. The code is available in a repository at GitHub: https://github.com/sciseim/GHSROS_MS.
- Grant note
- This work was supported by the National Health and Medical Research Council Australia (1002255 and 1059021; to Adrian Herington, Lisa Chopin and Inge Seim), the Cancer Council Queensland (1098565; to Adrian Herington, Rakesh Veedu, Lisa Chopin and Inge Seim), the Australian Research Council (grant no DP140100249; to Adrian Herington and Lisa Chopin), a QUT Vice-Chancellor’s Senior Research Fellowship (to Inge Seim), the Movember Foundation and the Prostate Cancer Foundation of Australia through a Movember Revolutionary Team Award, the Australian Government Department of Health, and the Australian Prostate Cancer Research Center, Queensland (Adrian Herington, Lisa K Chopin, Jenni Gunter, Elizabeth Williams and Colleen Nelson), Queensland University of Technology, the Instituto de Salud Carlos III (co-funded by European Union ERDF/ESF, “Investing in your future” grant no. PI13-00651; to Raúl Luque), a Miguel Servet grant (CP15/00156; to Manuel D. Gahete), Junta de Andalucía (grant no. BIO-0139 to R.M.L.), and CIBERobn (CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; to Raúl Luque).
- Organisation Unit
- School of Health - Biomedicine; Cancer Research Cluster
- Language
- English
- Record Identifier
- 991100345502621
- Output Type
- Journal article
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- Oncology
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