pPe O p inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway

pPe O p 通过上调 miR-30b-5p 和下调 Rac1/Cdc42 通路抑制 HGC-27 细胞增殖、迁移和侵袭

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作者:Wenjun Xu, Zhenjie Fu, Yuqin Xu, Man Hei Cheung, Yan Chen, Meiai Lin, Hang Wen, Hang Lv, Chun Liang, Jianshu Lou, Yitao Chen

Abstract

Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide. A bioactive protein (pPe Op) from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells. miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPe Op. Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPe Op treatment. Additionally, miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues. Following pPe Op treatment and/or transfection with miR-30b-5p mimic, the proliferation, migration, and invasion of HGC-27 cells are significantly impaired. Immunofluorescence microscopy shows that pPe Op and/or miR-30b-5p destroy(s) microfilaments and microstructures and inhibit(s) the formation of pseudopodia. Bioinformatics analysis, dual-luciferase reporter assay, and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A. Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPe Op. pPe Op upregulates miR-30b-5p expression, which in turn inhibits RAB22A expression, resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets, thus destroying the cytoskeletal structure and inhibiting the proliferation, migration, and invasion of cancer cells.

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