Whole-transcriptome Sequencing Combined With Single-cell Data In Exploring The Mechanisms Of CircRNA In Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma（NPC）is a malignant epithelial tumor that occurs on the nasopharyngeal mucosa and is commonly found on the top,sidewall,and pharyngeal crypts of the nasopharynx.According to the data of the World Health Organization,NPC is divided into three pathological subtypes,including keratinizing squamous cell carcinoma,non-keratinizing carcinoma and basal-like squamous cell carcinoma.According to the statistics from the International Agency for Research on Cancer,in 2018,approximately 129,000 new NPC cases were diagnosed globally accounting for 0.7% of all cancer cases.The incidence of NPC has obvious regional distribution,mainly in East Africa and Asia.The south of China is a high incidence area of nasopharyngeal carcinoma,such as Guangdong,Guangxi and Fujian.Nasopharyngeal cancer affects three out of every 100,000 people each year.Therefore,it is urgent to explore the risk factors of NPC.It is believed that many effects,including EBV,host genetics and environments are vital factors for the occurrence and development of NPC,especially the relationship between EBV and non-keratinizing carcinoma is the most closely.Nasopharyngeal carcinoma is diagnosed by nasopharyngoscopy biopsy,EBV antibody titer test and magnetic resonance imaging.The EBV antibody titer tests in patients’ serum are commonly used for clinical diagnosis and prognostic evaluation.At present,surgery,chemotherapy,radiotherapy,and concurrent radio-chemotherapy are the common treatments for NPC.Although some progress has been made in radiotherapy and chemotherapy,30% of patients with NPC still suffer from local recurrence and distant metastasis.Reducing the local recurrence and distant metastasis of NPC patients has become an urgent and difficult task in the prevention and treatment of NPC.Therefore,exploring the mechanisms in the occurrence and development of NPC,identifying the key molecules in controlling NPC,and providing therapeutic strategies for the new therapeutic targets are of great significance for further improving the diagnosis,therapy,and prognosis of NPC patients.With the completion of the Human Genome Project and the rapid development of the era,high-throughput sequencing has caused great changes in biomedical research,which bring more possibility for exploring multiple omics in a more comprehensive and detailed manner.The combination of the second-generation sequencing technology and multiple omics analyses affects the continuous development of biomedical research and promotes the development of bioinformatics technology for fully mining and analyzing cancer data.Among them,whole transcriptome sequencing has become an important method to explore the changes of RNAs in cells,including m RNA,circ RNA and lnc RNA.In recent years,more and more evidence shows that circ RNA could act as a "sponge" of mi RNA,therefore regulating the expression of downstream target genes.Based on this,circ RNA plays an important role in gene expression regulation,physiology,pathology,and human diseases,especially the occurrence and development of tumors.This study mainly used the whole transcriptome sequencing data combined with single-cell sequencing data to mine essential genes and circ RNAs in the occurrence and development of NPC.In this study,the NPC single-cell sequencing data were grouped.The relationship between cell types and gene modules was analyzed with the weighted co-expression network to determine the important modules and genes.The whole transcriptome data were used for verification.Secondly,three kinds of software were used to search for potential circ RNAs,which probably bind to potential mi RNAs through prediction of mi Randa.Therefore,ce RNA regulatory networks were constructed.Finally,it was found that RPMS1 gene was significantly expressed in NPC tissues through analyses of EBV,and a variety of BART mi RNAs can be expressed in this gene.EBV may affect the transformation of epithelial cells into cancer cells through mi RNAs.Therefore,this study deeply explored the roles of BART mi RNAs in NPC and found that BART mi RNAs bind to various transcription factors.BART mi RNAs may affect the expressions of circ RNA by regulating the expressions of transcription factors,thereby indirectly regulating the entire ce RNA network.The above data were integrated to construct a Virus＿mi R/Human＿TF/human＿circ RNA/Human＿mi R/m RNA signaling network,which clarified the pathogenesis of NPC from a network perspective.This study may provide new ideas for the treatment of NPC.