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Published on: March 17, 2018
pPe Op inhibits HGC-27 cell proliferation, migration and invasion by upregulating miR-30b-5p and down-regulating the
Wenjun Xu1, Zhenjie Fu1, Yuqin Xu1
1School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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.
Insights
A bioactive protein from Omphalia lapidescens upregulates miR-30b-5p, inhibiting gastric cancer cell growth. This microRNA targets RAB22A, reducing Rac1/Cdc42 activation and cancer cell proliferation, migration, and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer is a leading cause of cancer-related death globally.
- Omphalia lapidescens contains bioactive compounds with potential anti-cancer properties.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
Purpose of the Study:
- To investigate the anti-gastric cancer effects of a bioactive protein (pPeOp) from Omphalia lapidescens.
- To identify the specific miRNA involved in the anti-cancer mechanism of pPeOp.
- To elucidate the molecular pathway through which pPeOp exerts its effects on gastric cancer cells.
Main Methods:
- miRNA deep sequencing and verification of miR-30b-5p expression.
- Cell proliferation, migration, and invasion assays in HGC-27 cells.
- Immunofluorescence microscopy to assess cytoskeletal changes.
- Bioinformatics analysis, dual-luciferase reporter assays, and Western blot to confirm target interactions.
Main Results:
- pPeOp treatment significantly upregulated miR-30b-5p in HGC-27 cells.
- miR-30b-5p was downregulated in clinical gastric cancer tissues.
- pPeOp and/or miR-30b-5p inhibited HGC-27 cell proliferation, migration, and invasion.
- miR-30b-5p was confirmed to target RAB22A, downregulating Rac1/Cdc42 expression and activation.
- Cytoskeletal disruption and inhibition of pseudopodia formation were observed.
Conclusions:
- miR-30b-5p mediates the anti-gastric cancer effects of pPeOp.
- The pPeOp/miR-30b-5p axis inhibits gastric cancer progression by targeting RAB22A and disrupting the actin cytoskeleton.
- These findings highlight miR-30b-5p as a potential therapeutic target for gastric cancer.
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