Abstract
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.
Highlights
Esophageal cancer, including esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC), is one of the most common types of cancer worldwide [1]
To explore the role of miR‐196a in ESCC progression, miR‐196a inhibitor or inhibitor negative control (NC) were transfected into EC109 cells, and cell proliferation and apoptosis were measured. miR‐196a inhibitor‐induced miR‐196a knockdown in EC109 cells was confirmed by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) (Fig. 2A)
The results of the MTT assay revealed that miR‐196a downregulation significantly inhibited EC109 cell proliferation (Fig. 2B); flow cytometric analysis revealed that miR‐196a downregulation did not affect EC109 cell apoptosis (Fig. 2C)
Summary
Esophageal cancer, including esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC), is one of the most common types of cancer worldwide [1]. A detailed study on the mechanisms underlying the development and progression of ESCC is required, in order to improve the prevention, diagnosis and treatment of this disease. It has previously been reported that miRNA dysregulation is involved in the development and progression of cancer [6]. Previous studies have revealed that miR‐196a is upregulated in various types of cancer, including ESCC [7,8,9]. Further studies have demonstrated that miR‐196a promotes tumor progression and acts as an oncogene in some types of cancer [10,11]. It has been reported that miR‐196a promotes cell proliferation and invasion by targeting homeobox A5 in non‐small cell lung cancer [12]. The role of miR‐196a in ESCC remains unclear
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