Abstract
Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16) mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN) tissues from three patients with high-throughput RNA sequencing (RNA-seq). In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE) in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO) terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA) network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer.
Highlights
Cervical cancer is the third most common type of cancer and the fourth leading cause of cancer-associated mortality in women, with an estimated 526,000 new cases and 239,000 deaths in 2015 globally (Fitzmaurice et al, 2017)
We identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were DE between CSCC and ATN tissues using RNA-seq
For the first time we systematically reported the ceRNA network based on DE lncRNAs, circRNAs, miRNAs, and mRNAs
Summary
Cervical cancer is the third most common type of cancer and the fourth leading cause of cancer-associated mortality in women, with an estimated 526,000 new cases and 239,000 deaths in 2015 globally (Fitzmaurice et al, 2017). Cervical cancer is caused by a persistent infection with high-risk human papillomavirus (HPV), including HPV-16, HPV-18, and HPV-53. HPV16 and HPV18, the most frequently detected subtypes worldwide, contribute to 70% of all invasive cervical cancer cases (de Sanjose et al, 2010). In most cases, women infected by HPV remain asymptomatic because an adequate immune response is capable of controlling the infection, and very few cases progress to cervical cancer (Insinga et al, 2011). Previous studies have suggested that abnormal host genes as well as additional factors, such as multiparity and smoking, influence the risk of cervical cancer development (Vaccarella et al, 2006; Louie et al, 2011; de Freitas et al, 2014). The discovery of vital diagnostic and therapeutic molecular markers could offer substantial help in controlling the infection of HPV and preventing the progression of cervical cancer
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