脑 Ras 相关蛋白 4A（Rab4A）被 miR-496 下调以抑制胃癌的进展。
Ras-related Protein in Brain 4A (Rab4A) is Downregulated by miR-496 to inhibit the Progression of Gastric Cancer.
机构信息
Department of Gastrointestinal Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
Department of Pathogenic Biology, Chengde Medical University, Chengde 067000, Hebei, China.
出版信息
Comb Chem High Throughput Screen. 2024;27(18):2734-2740. doi: 10.2174/0113862073260841231010055245.
INTRODUCTION
Ras-related protein in brain 4A (Rab4A), as a member of the Rab family, is involved in the intracellular circulation of membrane receptors or endocytic substances and regulates the progression of multiple tumors.
METHODS
From our results, the knockdown of Rab4A inhibited the proliferation, migration and invasion in AGS cells. Importantly, the surface expression of epidermal growth factor receptor (EGFR) declined significantly in Rab4A knockdown cells. The downstream pathway of EGFR was also inhibited after the transfection of Rab4A-specific siRNA, including AKT and β-catenin pathways.
RESULT
In addition, miR-496 down-regulated the expression of Rab4A in AGS cells. The result of the luciferase reporter assay showed that miR-496 could bind to the 3'UTR of Rab4A.
CONCLUSION
In conclusion, the expression of Rab4A is inhibited by miR-496, and the knockdown of Rab4A inhibits the proliferation, migration and invasion through down-regulating the surface expression of EGFR. Rab4A is a potential target in the treatment of gastric cancer.
简介
脑中 Ras 相关蛋白 4A（Rab4A）作为 Rab 家族的一员，参与膜受体或内吞物质的细胞内循环，并调节多种肿瘤的进展。
方法
从我们的结果来看，Rab4A 的敲低抑制了 AGS 细胞的增殖、迁移和侵袭。重要的是，Rab4A 敲低细胞中表皮生长因子受体（EGFR）的表面表达显著下降。转染 Rab4A 特异性 siRNA 后，EGFR 的下游通路也被抑制，包括 AKT 和 β-连环蛋白通路。
结果
此外，miR-496 在 AGS 细胞中下调 Rab4A 的表达。荧光素酶报告基因检测结果表明，miR-496 可以结合 Rab4A 的 3'UTR。
结论
总之，miR-496 抑制 Rab4A 的表达，敲低 Rab4A 通过下调 EGFR 的表面表达抑制增殖、迁移和侵袭。Rab4A 是胃癌治疗的潜在靶点。
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