Poster Presentation Women's Health Forum 2021

Harnessing the Long non-coding RNA Encoded Micropeptidome in High-grade Serous Ovarian Carcinoma (#31)

Chamikara Liyanage 1 2 , MohammedAdil Malik 1 2 , Jyotsna Batra 1 2
  1. School of Biomedical Sciences, Faculty of Health, Queensland University Of Technology, Brisbane, QLD, Australia
  2. Translational Research Institute, Woolloongabba, QLD, Australia

High-grade serous ovarian carcinoma (HGSOC) is the most common and most lethal histological type of ovarian cancer. Alternations in HGSOC genome, transcriptome, and proteome have been characterised by The Cancer Genome Atlas (TCGA) program, providing the foundation for linking HGSOC genotype/proteotype to its phenotype. Recent studies provide evidence of differential long noncoding RNA (lncRNA) expression and their association with cancer and response to therapy. Also, lncRNAs may have small-open reading frames (sORFs) that code for ‘hidden’ micropeptides (<100 amino acids) emerging as indispensable regulatory elements independent of lncRNA’s function as RNA. In the current study, we investigated the lncRNA encoded micropeptidome of HGSOC, via applying a novel proteogenomic approach on mass spectrometry data of TCGA HGSOC tissue specimens (n = 103) and HGSOC cell lines (n = 4). Intriguingly, 28 novel lncRNA-encoded micropeptides were identified expressed in both HGSOC tissue specimens and cell lines. In-silico CPPred-sORF analysis predicted the coding potential of sORFs (23/28) based on canonical/non-canonical start sites and other sequence features. One-third (13/28) of lncRNAs coding for micropeptides were found conserved among vertebrates, indicating their maintenance throughout evolution and possible involvement in biological functions. By performing SWATH-mass spectrometry analysis of HGSOC cell lines (n = 4) we experimentally validated the expression of novel micropeptides. The hierarchical-clustering analysis led to the classification of differentially expressed micropeptides that coincided with the clinical stratifications, such as tumour subtype, grade, stage, and platinum-state. Furthermore, Kaplan-Meier survival analysis identified micropeptides (5/28) low expression of which was significantly correlated with the poor overall survival of HGSOC patients. Taken together, our study provides the first evidence of the differential abundance of lncRNA-encoded micropeptides in HGSOC, underlying their prognostic potential to serve as biomarkers. Further functional studies will improve the mechanistic understanding of micropeptides in HGSOC, supporting future identification of innovative therapeutic approaches for HGSOC.