title: Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues.
abstract: Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells.
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Agnes T
authors.initials: AT
authors.lastname: Reiner
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Auer
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Nyamdelger
authors.initials: N
authors.lastname: Sukhbaatar
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachleitner-Hofmann
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Mesteri
authors.affiliation: Department of Medicine I, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Oncology, Vienna, Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Grunt
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Department of Obstetrics and Gynaecology, Molecular Oncology Group, Comprehensive Cancer Centre, Medical University of Vienna &Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018938:Caco-2 Cells; D002460:Cell Line; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008171:Lung Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000378:metabolism*; D000079962:RNA, Circular; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D000079962:RNA, Circular; D012313:RNA; D005095:Exoribonucleases; C080868:ribonuclease R