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

PeerJ

article

Patrick B. Thomas¹  Penny Jeffery¹  Manuel D. Gahete⁴  Eliza Whiteside⁹  Carina Walpole¹  Michelle Maugham¹  Lidija Jovanovic³  Jennifer Gunter³  Elizabeth Williams³  Colleen Nelson³  Adrian Herington¹  Raul M. Luque⁴  Rakesh Veedu^1,11  Lisa K. Chopin¹  Inge Seim¹ 

[1] Ghrelin Research Group, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology;Comparative and Endocrine Biology Laboratory, Translational Research Institute, School of Biomedical Sciences, Queensland University of Technology;Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology;Maimonides Institute of Biomedical Research of Cordoba;Department of Cell Biology, Physiology and Immunology, University of Cordoba;Hospital Universitario Reina Sofía;Campus de Excelencia Internacional Agroalimentario;CIBER de la Fisiopatología de la Obesidad y Nutrición;Centre for Health Research, University of Southern Queensland;Institute for Life Sciences and the Environment, University of Southern Queensland;Centre for Comparative Genomics, Murdoch University;Integrative Biology Laboratory, College of Life Sciences, Nanjing Normal University

关键词: Long non-coding RNA;    lncRNA;    Prostate cancer;    Antisense transcript;    Tumour growth;    Gene expression;   

DOI  :  10.7717/peerj.10280

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY