microRNA-33a prevents epithelial-mesenchymal transition, invasion, and metastasis of gastric cancer cells through the Snail/Slug pathway
microRNA-33a prevents epithelial-mesenchymal transition, invasion, and metastasis of gastric cancer cells through the Snail/Slug pathway
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DOI：
10.1152/ajpgi.00284.2018
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发表时间：
2019-08-01
影响因子：
4.5
通讯作者：
Huang, Ying-Peng
中科院分区：
文献类型：
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作者：
Chen, Di-Di;Cheng, Jiang-Ting;Huang, Ying-Peng
侵袭和转移是胃癌(GC)死亡的主要原因。MicroRNA-33a(miR-33a)可能在多种肿瘤中发挥抑癌作用。在这里，我们描述miR-33a在胃癌中的调节和功能，以及参与上皮-间充质转化(EMT)和转移的机制。首先收集胃癌组织和癌旁正常组织。采用MIR-33a上调或SNAI2耗竭的方法研究MIR-33a和SNAI2对GC细胞的调控机制。我们检测了miR-33a、SNAI2、Snail/Slug信号通路相关基因和EMT相关标记物在胃癌组织和细胞中的表达。检测MIR-33a在胃癌组织和癌旁正常组织中的分布。检测细胞增殖、迁移和侵袭能力，以及细胞周期分布。在裸鼠体内，观察到胃癌生长和淋巴结转移。此外，还评价了miR-33a对GC患者预后的预测价值。结果表明，胃癌组织中miR-33a低表达，SNAI2高表达，Snail/Slug活化，EMT增加。MIR-33a主要定位于细胞质。MIR-33a靶向和负调控的SNAI2。选择MKN-45和MKN-28细胞株进行体外实验。上调miR-33a的表达或siRNA介导的SNAI2沉默可抑制Snail/Slug的激活，从而抑制GC细胞的增殖、侵袭和迁移。急诊室。肿瘤生长和淋巴结转移均受到抑制。MiR-33a的高表达是影响胃癌预后的保护因素。本研究提示miR-33a通过调节SNAI2的表达，通过Snail/Slug信号通路抑制胃癌细胞的EMT、侵袭和转移。新发现值得关注的miR-33a靶向并抑制SNAI2的表达，SNAI2的过表达激活Snail/Slug信号通路，Snail/Slug信号通路促进胃癌细胞的增殖、侵袭和转移，miR-33a的过表达抑制细胞的增殖、侵袭和转移。本研究为GC的治疗提供了新的治疗靶点。
Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a) might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. First, GC tissues and adjacent normal tissues were collected. miR-33a upregulation or SNAI2 depletion on GC cells were introduced to assess the detailed regulatory mechanism of them. We assessed the expression of miR-33a, SNAI2, Snail/Slug signaling pathway-related genes, and EMT-related markers in GC tissues and cells. miR-33a distribution in GC tissues and adjacent normal tissues was measured. Cell proliferation, migration and invasion, and cell cycle distribution were assessed. In nude mice, GC tumor growth and lymph node metastasis were observed. Furthermore, the predicative value of miR-33a in the prognosis of GC patients was evaluated. The obtained results indicated that lowly expressed miR-33a, highly expressed SNAI2, activated Snail/Slug, and increased EMT were identified in GC tissues. miR-33a was located mainly in the cytoplasm. miR-33a targeted and negatively regulated SNAI2. MKN-45 and MKN-28 cell lines were selected for in vitro experiments. Upregulated miR-33a expression or siRNA-mediated silencing of SNAI2 suppressed the activation of Snail/Slug, whereby GC cell proliferation, invasion and migration. EMT. tumor growth, and lymph node metastasis were inhibited. High expression of miR-33a was a protective factor influencing the prognosis of GC. This study suggests that miR-33a inhibited EMT, invasion, and metastasis of GC through the Snail/Slug signaling pathway by modulating SNAI2 expression.NEW & NOTEWORTHY miR-33a targets and inhibits the expression of SNAI2, overexpression of SNAI2 activates the Snail/Slug signaling pathway, the Snail/Slug signaling pathway promotes GC cell proliferation, invasion, and metastasis, and overexpression of miR-33a inhibits cell proliferation, invasion, and metastasis. This study provides a new therapeutic target for the treatment of GC.