Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/β-catenin Pathway

Abstract

Background

Aberrant expression of retinoic acid receptor α (RARα) was correlated with diverse carcinomas such as acute promyelocytic leukemia and colorectal carcinoma. Nevertheless, the function and mechanism of RARα in esophageal carcinoma (EC) remain unclear.

Aim

To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC.

Methods and Results

In immunohistochemistry study, RARα was overexpressed in human EC tissues, and its overexpression was closely related to the pathological differentiation, lymph node metastasis, and clinical stages in EC patients. Functionally, RARα knockdown suppressed the proliferation and metastasis of EC cells through downregulating the expression of PCNA, Ki67, MMP7, and MMP9, as well as enhanced drug susceptibility of EC cells to 5-fluorouracil and cisplatin. Mechanistically, RARα knockdown inhibited the activity of Wnt/β-catenin pathway through reducing the phosphorylation level of GSK3β at Ser-9 and inducing phosphorylation level at Tyr-216, which resulted in downregulation of its downstream targets such as MMP7, MMP9, and P-gP.

Conclusions

Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/β-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.

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