MicroRNA-135 inhibits gastric cancer metastasis by targeting SMAD2

Y. He, L. Wu, Y. Dai, J. Li, S. Liu

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xhfkzlls@163.com

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• Oncology

OBJECTIVE: The purpose of this study was to investigate whether microRNA-135 plays a role in the malignant progression of gastric cancer (GC) by regulating SMAD2 and its underlying mechanism.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-135 expression in tumor tissue specimens and paracancerous ones of 28 patients with GC, and the interplay between microRNA-135 level and clinical indexes and prognosis of GC patients was also analyzed. Subsequently, when negative control (NC) sequence or microRNA-135 mimics were transfected into GC cell lines, Cell Counting Kit-8 (CCK-8), transwell and wound healing assays were used to analyze the impact of microRNA-135 on proliferation and apoptosis of GC cells. Finally, the mechanism of microRNA-135 on the downstream gene SMAD2 was explored by a cell recovery experiment.

RESULTS: QRT-PCR results revealed that in tumor tissues of GC patients, the microRNA-135 level was conspicuously lower than that in the adjacent tissues, and the difference was statistically significant. The overall survival rate was lower in patients with low expression of microRNA-135 compared with patients with a high one. In addition, in the GC cell lines including BGC-823 and SGC-7901, the cell proliferation, as well as invasion and migration ability of microRNA-135 mimics group, was significantly decreased compared with the NC group. Moreover, the research verified that SMAD2 expression in GC cell lines and tissues was markedly increased and negatively correlated with microRNA-135 level. The cell recovery study found that overexpression of SMAD2 can offset the influence of microRNA-135 mimics on proliferation and metastasis of GC cells, thus affecting the malignant progression of GC.

CONCLUSIONS: In this work, microRNA-135 was found conspicuously associated with lymph node or distant metastasis and poor prognosis of GC patients. Additionally, microRNA-135 may inhibit the malignant progression of GC by targeted regulating SMAD2 expression.

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