miR-29a-3p-dependent COL3A1 and COL5A1 expression reduction assists sulforaphane to inhibit gastric cancer progression
| Autor: | Jining Liu, Qipeng Yuan, Hui-Min David Wang, Sichong Han, Zhe Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Regulator Mice Nude Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Isothiocyanates Stomach Neoplasms In vivo Cell Line Tumor medicine Animals Anticarcinogenic Agents Humans Pharmacology Mice Inbred BALB C Dose-Response Relationship Drug biology Chemistry Wnt signaling pathway food and beverages Cancer medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs Collagen Type III 030104 developmental biology Sulfoxides 030220 oncology & carcinogenesis Catenin Disease Progression biology.protein Cancer research Female Collagen Type V Dicer Sulforaphane |
| Zdroj: | Biochemical Pharmacology. 188:114539 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2021.114539 |
| Popis: | The antitumor properties of cruciferous vegetables are mainly due to their high content of isothiocyanates, and sulforaphane (SFA) is the most well-known compound. The aim of this study was to determine the mechanism of SFA inhibiting gastric cancer (GC) progression. After verifying SFA suppressing GC growth in vivo, we utilized the GSE79973 and GSE118916 datasets to identify the GC development signatures that overlap with the RNA-seq analysis in SFA-treated AGS cells. GSEA of the RNA-seq data indicated that SFA regulation of GC progression was related to extracellular matrix and collagens; thus, we identified COL3A1 and COL5A1 as the targets of SFA, which functioned as oncogenes. We found positive correlations between COL3A1 and COL5A1 expression in GC cells, and confirmed that miR-29a-3p is the common regulator of their expression. RNA immunoprecipitation assays based on Ago2, Dicer, and exportin-5 showed that SFA could promote mature miR-29a-3p generation. We also proved that SFA inactivated the Wnt/β-catenin pathway in GC cells in a miR-29a-3p-dependent manner. Overall, SFA boosts miR-29a-3p maturation to downregulate COL3A1 and COL5A1 and inactivate the Wnt/ β -catenin pathway to suppress GC progression. |
| Databáze: | OpenAIRE |
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