Hsa_circ_0023984 Regulates Cell Proliferation, Migration, and Invasion in Esophageal Squamous Cancer via Regulating miR-1294/PI3K/Akt/c-Myc Pathway

Abstract

Circular RNAs (circRNAs) exert an essential function in the tumorigenesis and progression of esophageal squamous cancer (ESCC). Nonetheless, the role and potential mechanism of circ_0023984 in ESCC are blurred. circRNA expression profile data from Gene Expression Omnibus (GEO) database was applied to analyze circRNAs that were differentially expressed between ESCC tissues and paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze circ_0023984 expression and miR-1294 expression in ESCC tissues and cells. Then a series of functional experiments were executed to validate the role of circ_0023984 and miR-1294 in modulating the proliferation, migration, invasion, and cell cycle progression of ESCC cells. Luciferase reporter experiment was performed to confirm the targeting relationship between circ_0023984 and miR-1294. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out with DAVID database. Western blot assay was utilized to detect phosphorylated-Akt (p-Akt) expression and c-Myc expression. circ_0023984 was remarkably upmodulated in ESCC tumor tissues and cell lines. circ_0023984 overexpression was correlated with advanced clinical stage and lymph node metastasis of ESCC patients. circ_0023984 overexpression remarkably enhanced ESCC cell proliferation, migration, invasion, and cell cycle progression, while knockdown of circ_0023984 showed the opposite effect. circ_0023984 was the molecular sponge of miR-1294. miR-1294 could significantly inhibit ESCC cell proliferation, migration, invasion, and induce cell cycle arrest at G0/G1 phase. circ_0023984 affected ESCC progression through regulating miR-1294 expression. The target genes of miR-1294 were associated with cell cycle arrest and PI3K-Akt signaling pathway. circ_0023984 upregulated the expression of p-Akt and c-Myc by repressing miR-1294. circ_0023984 facilitates the malignant biological behaviors of ESCC cells through inhibiting miR-1294 and activating PI3K/Akt/c-myc pathway.

Keywords: Esophageal squamous cancer; PI3K/Akt/c-myc pathway; circ_0023984; miR-1294.