MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2

Abstract

Background/Aims: MicroRNAs (miRNAs) are non-coding single stranded RNAs of 17-25 nucleotides in size, and their altered expression has been observed in various cancers. Previous studies have confirmed that miR-433-3p has effects on cancer cell proliferation, invasion, and migration, and its expression also correlates with sensitivity to chemotherapy. However, to date, there have been no studies on the biological functions of miR-433-3p in esophageal squamous cell carcinoma (ESCC). Methods: The Cell Counting Kit-8, transwell, and matrigel assays were used to test the effects of miR-433-3p and its predicted target, growth factor receptor-bound protein 2 (GRB2), on the proliferation, migration, and invasion of Eca109 and KYSE30 cells, two types of esophageal cancer cell lines. The miR-433-3p binding site in the 3′ untranslated region (UTR) region of GRB2 was predicted and verified using miRNA target site prediction software and structuring correct mutant examination. Western blotting and fluorescent quantitative PCR (FQ-PCR) techniques were employed to evaluate GRB2 expression. The inhibitory effects of miR-433-3p on tumor growth were investigated using a tumor xenograft model. Results: The binding site of miR-433-3p was identified in the 3′UTR region of GRB2. Western blotting and FQ-PCR showed that miR-433-3p inhibited the mRNA and protein expression of GRB2. Overexpression of GRB2 inhibited tumorigenesis in nude mice. MiR-433-3p overexpression inhibited the proliferation, migration, and invasion of ESCC cells by suppressing GRB2 gene expression. Conclusions: Our findings suggest that targeting miR-433-3p may have therapeutic benefits in ESCC.

Keywords

• Mir-433-3p
• Esophageal squamous cell carcinoma
• GRB2
• Proliferation
• Invasion