Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

A role for the long non-coding RNA GHRLOS in cancer (#159)

Esha T Shah 1 2 3 , Patrick B Thomas 1 2 3 , Penny L Jeffery 1 2 3 , Colleen C Nelson 3 , Manuel D Gahete 4 , Raúl M Luque 4 , Inge Seim 1 2 3 , Lisa K Chopin 1 2 3
  1. Ghrelin Research Group, Institute of Health and Biomedical Innovation-Translational Research Institute, Queensland University of Technology, Woollongabba, Queensland, Australia
  2. Comparative and Endocrine Biology Laboratory, Translational Research Institute - Institute of Health and Biomedical Innovation, Queensland University of Technology, Woollongabba, Queensland, Australia
  3. Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, , Woollongabba, Queensland, Australia
  4. Maimonides Institute of Biomedical Research of Cordoba; Department of Cell Biology, Physiology and Immunology, University of Córdoba; Hospital Universitario Reina Sofía; CIBER de la Fisiopatología de la Obesidad y Nutrición; Campus de Excelencia Internaci, Corduba, Spain

Long non-coding RNA (lncRNA) genes are abundant in the human genome, and many are recognised as oncogenes or tumour suppressors. We previously characterised the structure of GHRLOS, a gene on the opposite strand of the multifunctional ghrelin gene (GHRL), however, its expression and function in disease has not been described. Here, interrogating The Cancer Genome Atlas (TCGA), we reveal that GHRLOS is differentially expressed in a number of cancers. In particular, expression was elevated in endometrial cancer (1.2 - fold; P = 7.1 x 10-3, Welch's two-sample t-test; n = 24 vs. n = 175) and prostate cancer (1.2-fold; P = 3.7 x 10-6; n = 52 vs. n = 498) compared to normal tissues. By qRT-PCR (using commercial cDNA panels) we confirmed that GHRLOS expression is upregulated in endometrial cancer (1.96-fold, P = 0.005, Welch’s two-sample t-test; n = 5 vs. n = 17) and prostate cancer (2.46-fold, P = 0.0045, Welch’s two-sample t-test; n = 5 vs. n = 21) compared to normal tissues. Using siRNA against GHRLOS, initial studies revealed significantly reduced cell migration in the PC3 prostate cancer cell line (0.47-fold change, P = 0.042 Kruskal-Wallis test, n = 2). In contrast, forced GHRLOS overexpression increased migration and proliferation. Finally, we reveal that knockdown and overexpression of GHRLOS reciprocally regulates splicing of the overlapping, multifunctional ghrelin gene. Taken together, we show that the long non-coding RNA, GHRLOS, is differentially expressed in tumour tissue, and regulates cell migration and proliferation, possibly by modulating ghrelin peptide production. Targeting GHRLOS could provide a valuable and novel way to target the ghrelin axis in disease. Ongoing studies aim to validate in vitro functional results in complementary mouse xenograft models, and identify genes and pathways regulated by this lncRNA.