High-grade Ovarian Cancer Associated H/ACA snoRNAs Promote Cancer Cell Proliferation and Survival

• Published in: bioRxiv
• Main Authors: Faucher-Giguere, Laurence, Roy, Audrey, Deschamps-Francoeur, Gabrielle, Couture, Sonia, Nottingham, Ryan M, Lambowitz, Alan M, Scott, Michelle S, Sherif Abou Elela
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 25.08.2021; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Apoptosis; Cancer Biology; Cell growth; Cell migration; Cell proliferation; Cell survival; Enzymes; Intellectual property; Invasiveness; Non-coding RNA; Nucleoli; Ovarian cancer; Ovarian carcinoma; Patent applications; RNA modification; RNA processing; RNA-directed DNA polymerase; rRNA; snoRNA; Tumor cell lines; Tumors; Wound healing
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2021.08.24.457387

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the nature and extent of snoRNAs contribution to the biology of cancer cells remain largely unexplored. In this study, we examined the abundance patterns of snoRNA in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumours (SBT) and identified a subset of snoRNA associated with increased invasiveness. This subgroup of snoRNA accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumour aggressiveness. Remarkably, knockdown of HGSC-associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Wound healing and cell migration assays confirmed the requirement of these HGSC-associated snoRNA for cell invasion and increased tumour aggressiveness. Together our data indicate that H/ACA snoRNAs promote tumour aggressiveness through the induction of cell proliferation and resistance to apoptosis. Competing Interest Statement Thermostable Group II Intron Reverse Transcriptase (TGIRT) enzymes and methods for their use are the subject of patents and patent applications that have been licensed by the University of Texas and East Tennessee State University to InGex, LLC. AML and the University of Texas are minority equity holders in InGex, and AML, some members of AML's laboratory, and the University of Texas receive royalty payments from the sale of TGIRT enzymes and kits and from the licensing of intellectual property by InGex to other companies. The other authors declare no competing interests. Footnotes * https://www.ncbi.nlm.nih.gov/geo