Downregulation of long noncoding RNA breast cancer anti-estrogen resistance 4 inhibits cell proliferation, invasion, and migration in esophageal squamous cell carcinoma by regulating the microRNA-181c-5p/LIM and SH3 protein 1 axis

Abstract

ABSTRACT Recently, abnormal expression of long non-coding RNAs (lncRNAs) has been observed in esophageal squamous cell carcinoma (ESCC). In various human cancers, breast cancer anti‑estrogen resistance 4 (BCAR4) was reported to be highly expressed, while the biological roles of BCAR4 in ESCC remain unclear. In ESCC cells and tissues, BCAR4 and microRNA −181c-5p (miR-181c-5p) expression, and phosphorylated signal transducer and activator of transcription (p-STAT3) and COX2 expression were evaluated by real-time reverse transcription PCR (qRT-PCR) and Western blot analysis. Cell function was evaluated by colony formation, CCK-8 assay, transwell and flow cytometer assays. Interactions between BCAR4 and miR-181c-5p, as well as miR-181c-5p and LIM and SH3 protein 1 (LASP1) were evaluated by RIP and luciferase reporter assay. ESCC cell malignancy with inhibition of BCAR4 was confirmed by a tumor xenograft model in vivo. In both ESCC tissues and cell lines, BCAR4 was upregulated. Downregulation of BCAR4 effectively induced cell apoptosis and inhibited invasion and migration in vitro, and reduced tumorigenesis in nude mice. BCAR4 was a sponge of miR-181c-5p to upregulate LASP1. Moreover, knockdown of BCAR4 and overexpression of miR-181c-5p inhibited the activation of the STAT3/COX2 signaling, which was reversed by overexpression of LASP1. In conclusion, BCAR4 promotes ESCC tumorigenesis by targeting the miR-181c-5p/LASP1 axis, which may act as a treatment and diagnosis biomarker for ESCC.