RNA sequencing reveals the implication of the circRNA-associated ceRNA network in oesophageal squamous cell carcinoma

Carcinogenesis. 2023 Oct 20;44(7):596-609. doi: 10.1093/carcin/bgad050.

Abstract

Circular RNAs (circRNAs) have attracted increasing attention in cancer research. However, there are few studies about the high-throughput sequencing for clinical cohorts focussing on the expression characteristics and regulatory networks of circRNAs in oesophageal squamous cell carcinoma (ESCC) until now. Present study aim to comprehensively recognize the functional and mechanistic patterns of circRNA through constructing a circRNA-related competing endogenous RNA (ceRNA) network in ESCC. Summarily, RNA high-throughput sequencing was adopted to assess the circRNA, miRNA and mRNA expression profiles in ESCC. Through bioinformatics methods, a circRNA-miRNA-mRNA coexpression network was constructed and hub genes was identified. Finally, cellular function experiments combined with bioinformatics analysis were conducted to verify the identified circRNA was involved in the progression of ESCC through ceRNA mechanism. In this study, we established a ceRNA regulatory network, including 5 circRNAs, 7 miRNAs and 197 target mRNAs, and 20 hub genes were screened and identified to exert important roles in the progression of ESCC. As a verification, hsa_circ_0002470 (circIFI6) was revealed to be highly expressed in ESCC and regulate the expression of hub genes by absorbing miR-497-5p and miR-195-5p through ceRNA mechanism. Our results further indicated that silencing of circIFI6 repressed proliferation and migration of ESCC cells, highlighting the tumour promotion effects of circIFI6 in ESCC. Collectively, our study contributes a new insight into the progression of ESCC from the perspective of the circRNA-miRNA-mRNA network, shedding light on the circRNA research in ESCC.