MicroRNA-663a upregulation upon ARID1A depletion promotes the growth and migration of esophageal cancer cells by targeting FKBP8.

Abstract

Background: ARID1A loss has been shown to promote the development and progression of cancers by modulating different target genes, including microRNAs (miRs). This study was performed to identify ARID1A-regulated miRs involved in esophageal cancer progression.

Methods: ARID1A expression in esophageal cancer cell lines was knocked down and the expression of candidate miRs that were differentially expressed between esophageal cancer and adjacent normal tissues was examined. The role of ARID1A-regulated miRs in the growth and migration of esophageal cancer cells was determined.

Results: ARID1A knockdown caused a significant upregulation of miR-663a in SKGT4 and EC109 esophageal cancer cells. Compared to normal tissues, esophageal cancer samples expressed higher levels of miR-663a. According to the Kaplan-Meier plotter database, high miR-663a expression was significantly associated with poor prognosis in esophageal cancer. Functional studies indicated that miR-663a overexpression promoted the growth, migration, and tumorigenesis of esophageal cancer cells. Silico analysis and dual luciferase reporter assays identified FKBP8 as a target for miR-663a. Knockdown of FKBP8 significantly increased the proliferation, colony formation, and migration capacities of esophageal cancer cells. Most importantly, miR-663a-induced aggressive phenotype in esophageal cancer cells relied on the repression of FKBP8 expression.

Conclusions: The miR-663a/FKBP8 axis regulated by ARID1A plays a critical role in esophageal cancer cell proliferation and migration and represents a potential therapeutic target for this malignancy.