Correlation of circular RNA abundance with proliferation – exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues

By Anna Bachmayr-Heyda, Agnes T. Reiner, Katharina Auer, Nyamdelger Sukhbaatar, S. Aust, T. Bachleitner-Hofmann, I. Mesteri, T. Grunt, R. Zeillinger, Dietmar Pils. Scientific Reports, 2015

703 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/99340797db179c9919eae822e463bd48a47e7683

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In Cancer Research

1. Igor Ulitsky
2. Stas Wüst
3. Sebastian Kadener
4. I. Patop

In Molecular Biology

1. Igor Ulitsky
2. Stas Wüst
3. Sebastian Kadener
4. Y. Yarden
5. I. Patop
6. M. Lacouture

Citations in the corpus

• Circular RNA: metabolism, functions and interactions with proteins (2020, result): “In contrast, another study reported a global reduction in circRNA abundance in highly proliferative tissues, possibly due to dilution by proliferation [54].”
• Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor (2015, background): “Thus, our study adds several hundreds of mammary circRNAs to the growing catalog of annotated circRNAs (8,12,13,15,16,28,47,56,57).”
• Past, present, and future of circRNAs (2019, positive): “These findings were in line with previous work that had suggested a negative correlation between circRNA levels and cell division rates (Bachmayr-Heyda et al , 2015).”
• Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “Mutational analysis has revealed that ~100 nt of each repeat is sufficient for exon circularization, even when there is competition between canonical splicing and back-splicing [21, 39].”
• CircRNA: a novel type of biomarker for cancer (2017, background): “Furthermore, through data set analysis, it is found that there are 39 circRNAs significant, abnormal expressions, and eleven circRNAs of them are overexpressions and twenty-eight of them are downexpressions in cancer [23].”