期刊
JOURNAL OF GASTROENTEROLOGY
卷 53, 期 6, 页码 725-739出版社
SPRINGER JAPAN KK
DOI: 10.1007/s00535-017-1408-0
关键词
Gastric cancer; miR-324-3p; Smad4; Wnt; Organoid
资金
- National Natural Science Foundation of China [81572362]
- National Natural Science Foundation Project of International Cooperation (NSFC-NIH) [81361120398]
- Primary Research & Development Plan of Jiangsu Province [BE2016786]
- Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [JX10231801]
- 333 Project of Jiangsu Province [BRA2015474]
- Jiangsu Key Medical Discipline (General Surgery)
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
Background Emerging evidence suggested that miRNAs can function as oncogenes or tumor suppressors by regulating downstream target genes. miR-324-3p has been reported to function in several carcinomas, but its role in gastric cancer (GC) is still unknown. This study aims to explore the effects of miR-324-3p on the development of GC. Methods Expression of miR-324-3p was examined in GC cells and tissues by qRT-PCR. Effects of miR-324-3p on GC cells were evaluated by cell vitality assay, colony formation assay, cell migration assay, and flow cytometric assay. The dual luciferase assay was used to verify whether miR-324-3p could interact with the potential target genes. Western blot was used to assess the expression level of Smad4 and beta-catenin. Intracellular ATP level was also examined. The tumor xenografts were established using nude mice. A gastric organoid model was made from fresh stomach tissue. Results miR-324-3p was expressed at higher levels in the tumor tissues compared with adjacent normal tissues. Overexpression of miR-324-3p promoted cell growth, migration, and decreased apoptosis. miR-324-3p repressed the expression of Smad4, and loss of Smad4 activated the Wnt/beta-catenin signaling pathway. Overexpression of Smad4 rescued the effects of miR-324-3p on GC cells. The intracellular ATP level was upregulated with overexpression of miR-324-3p. miR-324-3p facilitated tumor cell colonization and growth in vivo and contributed to the growth of gastric organoids. Conclusions The results suggested that miR-324-3p promoted GC through activating the Smad4-mediated Wnt/beta-catenin signaling pathway. The miR-324-3p/ Smad4/Wnt signaling axis may be a potential therapeutic target to prevent GC progression.
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