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

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...

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Main Authors: Xu Wenjun, Fu Zhenjie, Xu Yuqin, Cheung Man Hei, Chen Yan, Lin Meiai, Wen Hang, Lv Hang, Liang Chun, Lou Jianshu, Chen Yitao
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-12-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022193
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author Xu Wenjun
Fu Zhenjie
Xu Yuqin
Cheung Man Hei
Chen Yan
Lin Meiai
Wen Hang
Lv Hang
Liang Chun
Lou Jianshu
Chen Yitao
author_facet Xu Wenjun
Fu Zhenjie
Xu Yuqin
Cheung Man Hei
Chen Yan
Lin Meiai
Wen Hang
Lv Hang
Liang Chun
Lou Jianshu
Chen Yitao
author_sort Xu Wenjun
collection DOAJ
description 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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spelling doaj.art-223f8b066c0a4f788264872a161228d22023-11-07T01:03:07ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-12-01541897190810.3724/abbs.202219320d259ccpPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathwayXu Wenjun0Fu Zhenjie1Xu Yuqin2Cheung Man Hei3Chen Yan4Lin Meiai5Wen Hang6Lv Hang7Liang Chun8Lou Jianshu9Chen Yitao10["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["Division of Life Science, Center for Cancer Research and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"]["Department of Gastrointestinal Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, China"]["Division of Life Science, Center for Cancer Research and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong, China","EnKang Pharmaceuticals (Guangzhou) Ltd., Guangzhou 510145, China"]["School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China"]["School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China","Division of Life Science, Center for Cancer Research and State Key Lab for Molecular Neural Science, The Hong Kong University of Science and Technology, Hong Kong, China"]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. https://www.sciengine.com/doi/10.3724/abbs.2022193gastric cancermiR-30b-5p<italic>Omphalia lapidescens</italic> Schroet.Rac1/Cdc42
spellingShingle Xu Wenjun
Fu Zhenjie
Xu Yuqin
Cheung Man Hei
Chen Yan
Lin Meiai
Wen Hang
Lv Hang
Liang Chun
Lou Jianshu
Chen Yitao
pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
Acta Biochimica et Biophysica Sinica
gastric cancer
miR-30b-5p
<italic>Omphalia lapidescens</italic> Schroet.
Rac1/Cdc42
title pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
title_full pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
title_fullStr pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
title_full_unstemmed pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
title_short pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the Rac1/Cdc42 pathway
title_sort ppe op inhibits hgc 27 cell proliferation migration and invasion by upregulating mir 30b 5p and down regulating the rac1 cdc42 pathway
topic gastric cancer
miR-30b-5p
<italic>Omphalia lapidescens</italic> Schroet.
Rac1/Cdc42
url https://www.sciengine.com/doi/10.3724/abbs.2022193
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