Abstract
Gene fusions and their products (RNA and protein) have been traditionally recognized as unique features of cancer cells and are used as ideal biomarkers and drug targets for multiple cancer types. However, recent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can also be found in normal cells and tissues. In this study, we aim to identify chimeric RNAs in different non-neoplastic cell lines and investigate the landscape and expression of these novel candidate chimeric RNAs. To do so, we used HEK-293T, HUVEC, and LO2 cell lines as models, performed paired-end RNA sequencing, and conducted analyses for chimeric RNA profiles. Several filtering criteria were applied, and the landscape of chimeric RNAs was characterized at multiple levels and from various angles. Further, we experimentally validated 17 chimeric RNAs from different classifications. Finally, we examined a number of validated chimeric RNAs in different cancer and non-cancer cells, including blood from healthy donors, and demonstrated their ubiquitous expression pattern.
Highlights
IntroductionRecent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can be found in normal cells and tissues
HEK-293T is established from human embryonic kidney, HUVEC is a human umbilical vein endothelial cell line, and LO2 is a human hepatocyte line
Similar to our previous publication [34], we categorized chimeric RNAs according to junction localization relative to parental genes: both sides being known exon/intron boundaries (E/E), both sides falling into the middle of exons (M/M), and one side being exon/intron boundary and the other not (E/M or M/E)
Summary
Recent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can be found in normal cells and tissues. We examined a number of validated chimeric RNAs in different cancer and non-cancer cells, including blood from healthy donors, and demonstrated their ubiquitous expression pattern. Chimeric fusion RNAs and their encoded proteins were once thought to be features unique to cancer, some of which have been successfully used as cancer diagnostic markers and therapeutic targets [1–4]. Compared to non-cancer tissues and cells, most of these chimeric RNAs are significantly over-expressed in cancer. Without doubt, they represent effective markers for clinical diagnosis/prognosis, and/or drug targets.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
