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Anticancer bioactive peptide‑3 inhibits human gastric cancer growth by targeting miR‑338‑5p.
- Source :
-
Cell & Bioscience . 9/22/2016, Vol. 6, p1-12. 12p. 2 Charts, 5 Graphs. - Publication Year :
- 2016
-
Abstract
- Background: Cancer incidence and mortality have been increasing in China, making cancer the leading cause of death since 2010 and a major public health concern in the country. Cancer stem cells have been studied in relation to the treatment of different malignancies, including gastric cancer. Anticancer bioactive peptide-3 (ACBP-3) can induce the apoptosis of gastric cancer stem cells (GCSCs) and reduce their tumorigenicity. In the present study, for the first time, we used a miRNA microarray and bioinformatics analysis to identify differentially expressed miRNAs in ACBP-3- treated GCSCs and GCSC-derived tumors in a xenograft model and functionally verified the identified miRNAs. miR- 338-5p was selected based on its significant upregulation by ACBP-3 both in cultured GCSCs and in tumor tissues. Results: miR-338-5p was downregulated in GCSCs compared with normal gastric epithelial cells, and the ectopic restoration of miR-338-5p expression in GCSCs inhibited cell proliferation and induced apoptosis, which correlated with the upregulation of the pro-apoptotic Bcl-2 proteins BAK and BIM. We also found that ACBP-3-treated GCSCs could respond to lower effective doses of cisplatin (DDP) or 5-fluorouracil (5-FU), possibly because ACBP-3 induced the expression of miR-338-5p and the BAK and BIM proteins and promoted GCSC apoptosis. Conclusions: Our data indicate that miR-338-5p is part of an important pathway for the inhibition of human gastric cancer stem cell proliferation by ACBP-3 combined with chemotherapeutics. ACBP-3 could suppress GCSC proliferation and lower the required effective dose of cisplatin or 5-fluorouracil. Therefore, this study provides not only further evidence for the remarkable anti-tumor effect of ACBP-3 but also a possible new approach for the development of GCSC-targeting therapies. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANTINEOPLASTIC agents
*STOMACH cancer
*MICRORNA
Subjects
Details
- Language :
- English
- ISSN :
- 20453701
- Volume :
- 6
- Database :
- Academic Search Index
- Journal :
- Cell & Bioscience
- Publication Type :
- Academic Journal
- Accession number :
- 118359033
- Full Text :
- https://doi.org/10.1186/s13578-016-0112-8