Investigating the potential role for RBMY in cancer

Introduction: Head and neck squamous cell carcinoma (HNSCC), is a major healthcare concern with a high male prevalence. We hypothesise that the testis specific mRNA splicing regulator, Y-linked RBMY gene, is aberrantly expressed in HNSCC in part promoting HNSCC through ZFY-short splicing. RBMY has been shown to enhance tumour development in male hepatocellular carcinoma (human tissue specimens and transgenic-mouse models) whilst ZFY-short is predicted to have anti-apoptotic properties and the deletion of RBMY locus on Y-chromosome resulted in lowered ZFY-short expression. Thus, we hypothesize that ZFY-short is generated by RBMY and exerts its anti-apoptotic effects to promote male HNSCC. Methods: Due to the coronavirus lockdown, bench work was restricted to 6 months, therefore, I conducted an extended analysis of RBMY expression in human cancer, including a computational analysis of RBMY gene expression with data from the cBioPortal database. In my bench-work, I attempted to establish GFP- RBMY expressing cell lines and conducted fluorescence microscopy, RT- PCR and qPCR to analyse RBMY expression in HNSCC cell lines and its impact on ZFY-short expression. Results: RBMY is expressed in several cancers, with no driver mutations. RBMY has nuclear localisation and is expressed in 93-UV-147T and UM-SCC-104 cell lines (both HPV16-positive HNSCC cell lines), with increased ZFY-short expression observed in UM- SCC-104. Discussion: Despite RBMY having been shown to be an oncogene in male liver cancer, our analysis of cBioPortal data suggests this activity may be restricted to the small minority of tumours of different cancer types that express RBMY. The paralleled expression of RBMY and ZFY-short in our cell lines indicate an association. UMSCC104 cell line originates from a highly an aggressive and recurrent tumour, RBMY is associated with tumour stemness, thus it is possible that via ZFY-short, RBMY could have promoted the aggressive phenotype in this, and in other HNSCCs.