Poster Presentation Australasian RNA Biology and Biotechnology Association 2026 Conference

VIRMA amplification drives oncogenesis and chemoresistance in High Grade Serous Ovarian Cancer (#100)

Stephanie Adler 1 2 , Jessica Tieng 1 2 , Renhua Song 1 2 , Jemma Couillault 1 2 , Alex Cole 3 , Anna DeFazio2 2 4 5 , Justin Wong 1 2
  1. Epigenetics and RNA Biology Laboratory , Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia
  2. School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
  3. Centenary Institute and Faculty of Medicine and Health, Centenary Institute, Sydney, NSW, Australia
  4. The Westmead Institute for Medical Research, Westmead, NSW, Australia
  5. Department of Gynaecological Oncology, Westmead Hospital, Westmead , NSW, Australia

 

High grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer. Despite this, new advancements in treatment for patients with HGSOC have not been developed for over 40 years, since the introduction of platinum-based inhibitors. An emerging therapeutic target in cancer is N6-methyladenosine (m6A), which is the most prevalent RNA modification. m6A is deposited by specific writers (or methyltransferases) composed of catalytic and scaffolding proteins. Whilst the catalytic components of the writer complex have been widely studied, the importance of scaffolding proteins such as Vir-like m6A methyltransferase associated protein (VIRMA) is unknown in HGSOC.

 

We analysed HGSOC datasets from The Cancer Genome Atlas Program (TCGA, n=124) and a previously published cohort by Garsed et al. (n=124) and found VIRMA to have the highest frequency of gene amplification (10% and 15% respectively) out of all the writer components of m6A. VIRMA amplification was associated with a significant increase in VIRMA expression. Patients with VIRMA amplification had a worse median overall survival time in both cohorts (log rank-test, p<0.0001). High levels of VIRMA are significantly associated with resistance to traditional platinum-based chemotherapy in HGSOC. In vitro validation showed overexpression of VIRMA in HGSOC cell lines increased cell growth and colony formation. Conversely, knockdown of VIRMA impaired cell growth and colony formation. Nanopore DRS revealed estrogen response and interferon signaling as pathways that VIRMA regulates to promote oncogenesis. These findings suggest VIRMA as a driver of oncogenesis in HGSOC and may be a potential target for new treatments.