Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer

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.

RETRACTED: Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor

“…LncRNAs are a large subgroup of noncoding RNAs that have emerged as regulators of crucial processes in various human cancers including cervical cancer (Aalijahan and Ghorbian, 2019). In recent decades, multiple lncRNAs have been reported to be aberrantly expressed in cervical cancer, and their aberrant expression plays important roles in the aggressive phenotype of cervical cancer Dong et al, 2017;Wang et al, 2017). Hence, exploration of the detailed involvement of lncRNAs in cervical cancer and their mechanisms of action is necessary to discover promising targets for the diagnosis and treatment of patients with this cancer.…”

Improvement in RNA quantity and quality in cervico-vaginal cytology

“…Previous studies have demonstrated the important role of long non-coding RNAs, circular RNAs, microRNAs and mRNAs in cervical cancer development and progression [2][3][4]. High-quality RNA is a pre-requisite for gene expression studies.…”

Long Non-Coding RNA Signature in Cervical Cancer

“…A recent study aimed at identification of expression profiles of lncRNAs, circular RNAs, microRNA (miRNA), and messenger RNA (mRNA) in HPV16 mediated cervical squamous cell carci noma have found 19 lncRNAs that are frequently differentially expressed in cervical cancer samples compared to normal samples. Such differentially expressed lncRNAs have been shown to participate in cervical cancer pathogenesis as revealed by the co-expression network and function prediction [19]. In addition to this high throughput studies, several studies have assessed the significance of lncRNAs in cervical cancer pathogenesis.…”