The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype

Thomas, Patrick B. and Jeffrey, Penny and Gahete, Manuel D. and Whiteside, Eliza ORCID: https://orcid.org/0000-0001-9710-7987 and Walpole, Carina and Maugham, Michelle and Jovanovic, Lidija and Gunter, Jennifer and Williams, Elizabeth and Nelson, Colleen and Herington, Adrian and Luque, Raul M. and Veedu, Rakesh and Chopin, Lisa K. and Seim, Inge (2021) The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype. PeerJ, 9:e10280. pp. 1-29. ISSN 2167-8359

[img]
Preview
Text (Published Version)
peerj-10280.pdf
Available under License Creative Commons Attribution 4.0.

Download (6MB) | Preview

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.


Statistics for USQ ePrint 41010
Statistics for this ePrint Item
Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: Current - Institute for Resilient Regions - Centre for Health Research (1 Apr 2020 -)
Faculty/School / Institute/Centre: Current - Institute for Life Sciences and the Environment (1 Aug 2018 -)
Date Deposited: 02 Feb 2021 02:19
Last Modified: 02 Feb 2021 02:19
Uncontrolled Keywords: long non-coding RNA, antisense transcript, prostate cancer, tumour growth, gene expression
Fields of Research (2008): 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death
11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111207 Molecular Targets
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321101 Cancer cell biology
32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321108 Molecular targets
Socio-Economic Objectives (2008): E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Socio-Economic Objectives (2020): 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions
20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions
Funding Details:
Identification Number or DOI: https://doi.org/10.7717/peerj.10280
URI: http://eprints.usq.edu.au/id/eprint/41010

Actions (login required)

View Item Archive Repository Staff Only