Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting miR-338-5p.
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.
Department of Cell Biology, Capital Medical University, Beijing, China.
Zhiwei
Z
Xing
The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia China.
Lan
L
Yu
Clinical Medical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia China.
Xian
X
Li
Department of Cell Biology, Capital Medical University, Beijing, China ; Clinical Medical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia China.
Xiulan
X
Su
5-fluorouracil; Cisplatin; Microarray; miR-338-5p; miRNA
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