3 years ago

Tumor‐suppressive microRNA‐10a inhibits cell proliferation and metastasis by targeting Tiam1 in esophageal squamous cell carcinoma

Yatian Liu, Xiaojun Wang, Xuesong Jiang, Pengwei Yan, Liangliang Zhan, Huanfeng Zhu, Tingting Wang, Jing Wen

Abstract

Aberrant microRNAs (miRNAs) expressions could contribute to the progression of numerous cancers, including esophageal squamous cell carcinoma, while miR‐10a participates in multiple biological processes on cancers. However, the molecular mechanism of miR‐10a in esophageal squamous cell carcinoma (ESCC) has not been investigated. Herein, miR‐10a was significantly reduced in ESCC clinical tissues and ESCC cell lines (EC109 and TE‐3). In addition, immunohistochemistry indicated that the expressions of α‐SMA, Ki‐67, and PCNA in tumor tissues were higher than that of controls. In vitro, overexpression of miR‐10a dramatically suppressed cell proliferation and enhanced cell apoptosis, while the decrease of miR‐10a expressed the opposite outcome. Specially, overexpression of miR‐10a caused a G0/G1 peak accumulation. Moreover, miR‐10a also negatively regulated ESCC cell migration and invasion. Furthermore, targetscan bioinformatics predictions and the dual‐luciferase assay confirmed that Tiam1 was a direct target gene of miR‐10a. The statistical analysis showed Tiam1 was negatively in correlation with miR‐10a in ESCC patient samples. And silencing Tiam1 could lead to a decline on cell growth, invasion, and migration in ESCC cell lines, while it could enhance cell apoptosis and cause a G0/G1 peak accumulation. In vivo, it revealed that miR‐10a notably decreased the tumor growth and metastasis in xenograft model and pulmonary metastasis model. And it showed a lower expressions of Tiam1 in the miR‐10a mimics group by immunohistochemistry. Taken together the results, they indicated that miR‐10a might function as a novel tumor suppressor in vitro and in vivo via targeting Tiam1, suggesting miR‐10a to be a candidate biomarker for the ESCC therapy.

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