MicroRNA (miR)-196a is upregulated in various types of malignancy, including esophageal squamous cell carcinoma (ESCC); however, its role in ESCC is currently unclear. The present study aimed to investigate the biological role and molecular mechanism of miR-196a in ESCC. The expression levels of miR-196a in 25 tumor tissues and adjacent non-tumor tissues from patients with ESCC were measured by reverse transcription-quantitative polymerase chain reaction. In addition, miR-196a expression levels were assessed in the human normal esophageal epithelial cell line Het-1A and the ESCC cell line EC109. The effects of miR-196a on the proliferation, apoptosis, invasion and migration of EC109 cells were determined by MTT, flow cytometry and Transwell assays, respectively. A luciferase reporter assay and western blotting were performed to confirm the target gene of miR-196a, and to explore the molecular mechanism underlying the effects of miR-196a on regulation of ESCC cell phenotypes. The results demonstrated that miR-196a was markedly upregulated in ESCC tissues and EC109 cells. In addition, miR-196a downregulation suppressed EC109 cell proliferation, invasion and migration, but did not affect apoptosis. Annexin A1 (ANXA1) was demonstrated to be a direct target gene of miR-196a. ANXA1 protein knockdown reversed the effects of miR-196a inhibition on EC109 cell proliferation, invasion and migration. Furthermore, alongside the downregulation of miR-196a and the increase in ANXA1 expression, cyclooxygenase 2 (COX2), matrix metalloproteinase (MMP)-2 and Snail were downregulated, and E-cadherin was upregulated in EC109 cells. The results of the present study suggested that miR-196a may act as an oncogene in ESCC, and that miR-196a may regulate the proliferation, invasion and migration of ESCC cells by targeting ANXA1. Subsequently, ANXA1 may further modulate the expression levels of COX2, MMP-2, Snail and E-cadherin. In conclusion, the miR-196a/ANXA1 axis may represent a potential therapeutic target in ESCC.
Keywords: Annexin A1; cell invasion; cell migration; cell proliferation; esophageal squamous cell carcinoma; microRNA-196a.