A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress

• 作者: Andreas W.Heumüller Antonella Di Liddo Camila de Oliveira Freitas Machado Julia E.Weigand Kathi Zarnack Michaela Müller-McNicoll Sandra Fischer Stefanie Ebersberger
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2019,（10）
• 页码范围: 829-844
• 页数: 16页
• 语种: 英文
• DOI: 10.1093/jmcb/mjz094

摘要

Hypoxia is associated with several diseases,including cancer.Cells that are deprived of adequate oxygen supply trigger transcriptional and post-transcriptional responses,which control cellular pathways such as angiogenesis,proliferation,and metabolic adaptation.Circular RNAs (circRNAs) are a novel class of mainly non-coding RNAs,which have been implicated in multiple cancers and attract increasing attention as potential biomarkers.Here,we characterize the circRNA signatures of three different cancer cell lines from cervical (HeLa),breast (MCF-7),and lung (A549) cancer under hypoxia.In order to reliably detect circRNAs,we integrate avaitable tools with custom approaches for quantification and statistical analysis.Using this consolidated computational pipeline,we identify ～ 12000 circRNAs in the three cancer cell lines.Their molecular characteristics point to an involvement of com plementary RNA sequences as well as trans-acting factors in circRNA biogenesis,such as the RNA-binding protein HNRNPC.Notably,we detect a number of circRNAs that are more abundant than their linear counterparts.In addition,64 circRNAs significantly change in abundance upon hypoxia,in most cases in a cell type-specific manner.In summary,we present a comparative circRNA profiling in human cancer cell lines,which promises novel insights into the biogenesis and function of circRNAs under hypoxic stress.