Abstract
Increasing evidence suggests that circular RNA (circRNA) plays an important role in tumorigenesis by regulating gene expression at the transcriptional and post-transcriptional levels. Alternative splicing events permit multiple transcript isoforms of circRNA to be produced; however, changes in the expression of circRNA full-length transcripts in cervical cancer remain unclear. Here, we systematically explored the dysregulation circRNA full-length transcripts and constructed an improved circRNA-miRNA-mRNA regulatory network to provide potential biomarkers and possible treatment targets in cervical cancer. We identified 9359 circular full-length transcripts from RNase R-treated RNA-seq data in cervical cancer, of which 353 circular full-length transcripts were significantly differentially expressed (DE) between the tumor and normal group. A total of 881 DE mRNA transcript isoforms were also identified from total RNA-seq data in cervical cancer, of which 421 (47.8%) transcript isoforms were up-regulated, and 460 (52.2%) transcript isoforms were down-regulated in tumor samples. Two circRNA-miRNA-mRNA competitively regulated networks, including 33 circRNA transcripts, 2 miRNAs, and 189 mRNA transcripts were constructed. Three genes (COPE, RAB3B, and TFPI) in the network were significantly associated with overall survival (P < 0.05), which indicated that these genes could act as prognostic biomarkers for patients with cervical cancer. Our study revealed genome-wide differential expression of full-length circRNA transcripts and constructed a more accurate circRNA-miRNA-mRNA network at the full-length transcript expression level in cervical cancer. CircRNA may thus be involved in the development of cervical cancer by regulating the expression of COPE, RAB3B, and TFPI. However, the specific regulatory mechanism in cervical cancer requires further study.
Highlights
Cervical cancer is the fourth most common type of cancer diagnosed in women (Bray et al, 2018) and the fourth main cause of cancer mortality in women; cervical cancer poses a serious threat to the health of women worldwide
According to the chromosomal location of circRNAs, we concluded that 82.8% of circRNAs were derived from exonic regions and 10.7% of circRNAs were derived from intronic regions; only 6.5% of circRNAs were derived from intergenic regions
We used CircAST software to assemble and quantify the full-length transcripts of the circRNA derived from exons in cervical cancer
Summary
Cervical cancer is the fourth most common type of cancer diagnosed in women (Bray et al, 2018) and the fourth main cause of cancer mortality in women; cervical cancer poses a serious threat to the health of women worldwide. Statistics from the Global Cancer Annual Report from 2018 revealed that there were approximately 570,000 new cases of cervical cancer and that approximately 311,000 cancer patients died of cervical cancer (Bray et al, 2018). Cervical cancer is the sixth most common cause of female malignant tumors, accounting for 6.25% of cases. In China, there are approximately 100,000 new cases of cervical cancer and 30,000 deaths from cervical cancer annually. Current treatment methods for cervical cancer include surgery, radiotherapy, chemotherapy, and comprehensive treatment. Patients with advanced cervical cancer have lost the opportunity for surgical resection because of tumor metastasis and cannot bear the side effects of radiotherapy and chemotherapy (Cohen et al, 2019). There is a need to explore the internal mechanism of cervical cancer and identify new therapeutic targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
