Construction of circRNA-Associated ceRNA Network Reveals Novel Biomarkers for Esophageal Cancer

Abstract

Objective. Esophageal cancer (ESCC) is reported to be the eighth most common malignant tumors worldwide with high mortality. However, the functions of majority circRNAs in ESCC requires to be further explored. Methods. This study identified differently expressed circRNAs in 3 paired ESCC using RNA-sequencing method. The interactions among circRNAs, miRNAs, and mRNAs were predicted using bioinformatics analysis. Results. In this study, using RNA-sequencing method and integrated bioinformatics analysis, 418 overexpressed circRNAs and 637 reduced circRNAs in ESCC sample were identified. Based on the mechanism that circRNAs could play as ceRNAs to modulate targets expression, circRNA-miRNA and circRNA-miRNA-mRNA networks were constructed in this study. Based on the network analysis, 7 circRNAs, including circ_0002255, circ_0000530, circ_0001904, circ_0001005, circ_0000513, circ_0000075, and circ_0001121, were identified as key circRNAs in ESCC. We found that circ_0002255 was related to the regulation of substrate adhesion-dependent cell spreading. circ_0001121 was involved in regulating nucleocytoplasmic transport. circ_0000513 played a key role in regulating Adherens junction, B cell receptor signaling pathway. Meanwhile, we observed circ_0000075 was involved in regulating zinc II ion transport, transition metal ion homeostasis, and angiogenesis. Conclusion. We thought this study could provide novel biomarkers for the prognosis of ESCC.

circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

“…19,20 Studies have also demonstrated that the imbalance of circRNA levels exerts essential function in regulating EC development. 8,21 However, the effects of circFIG 4 on EC development have not been investigated. Here, we attested that circFIG 4 level was enhanced in EC.…”

“…[4][5][6] In recent years, diverse cir-cRNAs have been illuminated to be abnormally expressed in tumors and linked to the pathogenesis of human cancers by interacting with microRNAs (miRNAs), 7 including EC. 8 For example, circ-PRMT5 promoted the metastasis of EC by binding to miR-203. 9 circFIG 4 (also termed as hsa_circ_0077607), derived from FIG 4 precursor mRNA, was located at chr6: 110036280-110 064 975.…”

Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

“…2 Pivotal players of ESCC pathogenesis, including proteins and circular RNAs (circRNAs), are being intensively explored. [3][4][5] Knowing the functions of these players may contribute to developing targeted and personalized therapy in further medicine.…”

“…7,8 Recently, circRNAs have established roles via their ceRNA activity in impacting the establishment and progression of human tumors, 9 including ESCC. 4,5,10 Human circ_0001946 is originated in a process called back-splicing of exons of cerebellar degeneration related protein 1 (CDR1) and it has established a contradictory role in tumor biology. [11][12][13] Circ_0001946 is present at low levels in glioblastoma and lung cancer and it operates as a potential anti-tumor factor in these cancers.…”

Significance of Circular FAT1 as a Prognostic Factor and Tumor Suppressor for Esophageal Squamous Cell Carcinoma

“…8,9 Regarding ESCC, as well as other cancers, circRNAs with the potential to serve as novel biomarkers have been examined in recent years and their number is increasing. [10][11][12][13][14][15][16] Circular FAT1 (circFAT1, circ_0001461) is a noncoding RNA with a cyclic structure that is formed by the back-splicing of exon 2 of the FAT1 gene and head-to-tail binding. Its expression and oncological significance were initially reported for osteosarcoma in 2018 17 and subsequent studies reported similar findings for other cancer types.…”