Mir-378a-3p Exerts Tumor Suppressive Function On The Tumorigenesis Of Esophageal Squamous Cell Carcinoma By Targeting Rab10

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE(2018)

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摘要
Esophageal squamous cell carcinoma (ESCC) is a life-threatening cancer with increasing incidence worldwide. MicroRNAs (miRs) have been reported to be involved in the progression of various types of cancer. In previous studies, the expression of miR-378a-3p was shown to be reduced in ESCC tissues. However, the mechanism underlying the effect of miR-378a-3p in ESCC remains to be elucidated. By employing a reverse transcription-quantitative polymerase chain reaction, miR-378a-3p expression was tested in ESCC tissues and cell lines. In addition, the effects of miR-378a-3p on cell viability, proliferation, apoptosis, migration and invasion were studied using an MTT assay, an EdU assay, flow cytometry analysis, wound healing analysis and a Transwell assay. In the present study, the level of miR-378a-3p was significantly downregulated in ESCC clinical tissues and cell lines (EC109 and KYSE150). In addition, the overexpression of miR-378a-3p suppressed the viability, proliferation, migration and invasion of the ESCC cells. The upregulated expression of miR-378a-3p also increased the expression levels of B-cell lymphoma 2-associated X protein and caspase-3, and decreased the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9, which attenuated ESCC tumorigenesis. Furthermore, Rab10 was confirmed to be a direct target gene of miR-378a-3p, and was negatively affected by miR-378a-3p. The silencing of Rab10 revealed antitumor effects in ESCC cell lines, and the expression of miR-378a-3p was negatively correlated with that of Rab10 in ESCC. Collectively, miR-378a-3p may act as a tumor-suppressor in ESCC cells through negatively regulating Rab10.
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关键词
microRNA-378a-3p, proliferation, migration, invasion, esophageal squamous cell carcinoma, Rab10
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