Identification of differentially expressed circular RNAs in human nasopharyngeal carcinoma

Article type: Research Article

Authors: Wu, Hanwei^{a; b; 1} | Liu, Yuchen^{a; b; 1} | Duan, Hongfang^{c; 1} | Fan, Xiaoqin^{a; b} | Wang, Yujie^{a; b} | Song, Jian^{a; b} | Han, Jinghong^{a; b} | Yang, Ming^d | Lu, Lu^a | Nie, Guohui^{a; b; *}

Affiliations: [a] Department of Otolaryngology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, Guangdong, China | [b] Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, Guangdong, China | [c] Department of Otolaryngology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, China | [d] Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong, China

Correspondence: [*] Corresponding author: Guohui Nie, Department of Otolaryngology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, Guangdong 518035, China. E-mail: nghui@21cn.com.

Note: [1] Hanwei Wu, Yuchen Liu and Hongfang Duan contributed equally to this work.

Abstract: BACKGROUND: Circular RNAs (circRNAs) are endogenous RNAs that have a covalent closed cycle configuration. circRNAs have been found to be differentially expressed in many human cancers. Therefore, circRNAs may be ideal biomarkers for the diagnosis and treatment of cancer. However, we know very little about the function of circRNAs in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the circRNA expression profiles in NPC. METHODS: We utilized high-throughput RNA sequencing (RNA-Seq) to evaluate the circRNA expression profile in NPC A total of 13,561 unique circRNA candidates were detected. Selection of aberrantly expressed circRNAs was carried out using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. We carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to identify the biological functions of differentially expressed circRNAs. Moreover, bioinformatics analyses were implemented to predict the effects between circRNAs and cancer-related microRNAs (miRNAs), and we used Cytoscape to build a cancer-related circRNA-miRNA target gene map. Finally, to verify dysregulated circRNAs, quantitative real-time PCR was utilized. RESULTS: In NPC tissues, we found that 73 circRNAs were downregulated and 59 were upregulated. The top 12 candidate circRNAs were selected from several vital NPC pathways such as the human papillomavirus and Epstein-Barr virus infection signaling pathways (hsa05165 and hsa05169, respectively), Hepatitis B (hsa05161), and the Ras signaling pathway (hsa04014). A network map of circRNA-miRNA interactions of 12 differentially expressed circRNAs was built. Hsa_circ_0007637 expression distinguished NPC tissues from paired healthy tissues and NPC cell lines (HNE1 6-10B, 5-8F, CNE-2, and so on) from a normal epithelial (NP460) cell line. CONCLUSIONS: In this study, we investigated the profiles of differentially expressed circRNAs in NPC, and our results show that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development. This observation-based research identified dysregulated circRNAs in NPC, which may assist in the development of biomarkers for this disease. Further studies on the mechanisms and functions of these circRNAs may promote our understanding of NPC tumorigenesis.

Keywords: CircRNAs, RNA-Seq, NPC, Hsa_circ_0007637

DOI: 10.3233/CBM-201731

Journal: Cancer Biomarkers, vol. 29, no. 4, pp. 483-492, 2020