Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer

Gregor Tevz; Sean McGrath; Ryan Demeter; Vincent Magrini; Varinder Jeet; Anja Rockstroh; Stephen McPherson; John Lai; Nenad Bartonicek; Jiyuan An; Jyotsna Batra; Marcel E Dinger; Melanie L Lehman; Elizabeth D Williams; Colleen C Nelson

doi:10.1016/j.mce.2015.10.011

Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer

Mol Cell Endocrinol. 2016 Jan 15:420:159-68. doi: 10.1016/j.mce.2015.10.011. Epub 2015 Oct 21.

Authors

Affiliations

¹ Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology/Translational Research Institute, Brisbane, QLD, Australia.
² McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
³ Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, Australia.
⁴ Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
⁵ Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology/Translational Research Institute, Brisbane, QLD, Australia; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
⁶ Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology/Translational Research Institute, Brisbane, QLD, Australia; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: colleen.nelson@qut.edu.au.

PMID: 26499396
DOI: 10.1016/j.mce.2015.10.011

Abstract

Simultaneous expression of highly homologous RLN1 and RLN2 genes in prostate impairs their accurate delineation. We used PacBio SMRT sequencing and RNA-Seq in LNCaP cells in order to dissect the expression of RLN1 and RLN2 variants. We identified a novel fusion transcript comprising the RLN1 and RLN2 genes and found evidence of its expression in the normal and prostate cancer tissues. The RLN1-RLN2 fusion putatively encodes RLN2 isoform with the deleted secretory signal peptide. The identification of the fusion transcript provided information to determine unique RLN1-RLN2 fusion and RLN1 regions. The RLN1-RLN2 fusion was co-expressed with RLN1 in LNCaP cells, but the two gene products were inversely regulated by androgens. We showed that RLN1 is underrepresented in common PCa cell lines in comparison to normal and PCa tissue. The current study brings a highly relevant update to the relaxin field, and will encourage further studies of RLN1 and RLN2 in PCa and broader.

Keywords: Fusion; Prostate cancer; RLN1; RLN2; RNA-Seq; SMRT sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androgens / pharmacology
Cell Line, Tumor
Exons / genetics
Humans
Male
Oncogene Proteins, Fusion / genetics*
Oncogene Proteins, Fusion / metabolism
Open Reading Frames / genetics
Prostatic Neoplasms / genetics*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Relaxin / genetics*
Relaxin / metabolism
Sequence Analysis, RNA

Substances

Androgens
Oncogene Proteins, Fusion
RNA, Messenger
Relaxin