Effect of pomegranate peel polyphenols on the malignant biological behavior of colon cancer cells by regulat-ing the miR-138-5p/HIF-1α pathway
10.3969/j.issn.1006-5725.2025.05.009
- VernacularTitle:石榴皮多酚调控miR-138-5p/HIF-1α通路对结肠癌细胞恶性生物学行为的影响
- Author:
Hongyan BIAN
1
;
Shu ZHANG
1
;
Shanshan MENG
1
;
Ying WEI
1
Author Information
1. 河南大学第一附属医院病理科(河南 开封 475000)
- Publication Type:Journal Article
- Keywords:
pomegranate peel polyphenols;
miR-138-5p/HIF-1α pathway;
colon cancer;
prolifera-tion;
apoptosis;
invasion;
migration
- From:
The Journal of Practical Medicine
2025;41(5):676-682
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of pomegranate peel polyphenols(PPP)on the malignant biological behavior of colon cancer cells through modulation of the miR-138-5p/hypoxia-inducible factor-1α(HIF-1α)pathway.Methods Quantitative real-time PCR(qRT-PCR)was employed to measure the expression levels of miR-138-5p and HIF-1α mRNA in the normal colon epithelial cell line FHC and three colorectal cancer cell lines:SW480,HCT116,and Caco-2.SW480 cells were divided into six groups:a blank control group,a negative control(mimics NC)group,a miR-138-5p mimics group,three different concentrations of PPP treatment groups(0.5 mg/mL,1 mg/mL,and 2 mg/mL),a PPP+inhibitor NC group at 2 mg/mL,and a PPP+miR-138-5p inhibitor group at 2 mg/mL.The effects on cell proliferation,invasion,and migration,as well as changes in apoptosis and related proteins including B-cell lymphoma 2(Bcl-2),migration invasion enhancer 1(MIEN1),and Cyclin D1,were evaluated separately.Additionally,the targeting relationship between miR-138-5p and HIF-1α was validated.The expression levels of miR-138-5p,HIF-1α mRNA,and protein were assessed in each experimental group.Results The expression levels of miR-138-5p were highest in FHC cells and lowest in SW 480 cells,while the expression levels of HIF-1α mRNA showed an opposite trend,being lowest in FHC cells and highest in SW 480 cells(P<0.05).Compared with the control group,different concentrations of PPP significantly promoted cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein,with significant differences between groups(P<0.05).Compared with the mimics NC group,the miR-138-5p mimics group significantly enhanced cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).Compared with the 2 mg/mL PPP+inhibitor NC group,the 2 mg/mL PPP+miR-138-5p inhibitor group significantly suppressed cell apoptosis,downregulated miR-138-5p expression,promoted cell proliferation,invasion,and migration,and upregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).These results indicate a targeted relationship between miR-138-5p and HIF-1α(P<0.05).Conclusion PPP inhibits the malignant biological behavior of colon cancer cells through upregulation of the miR-138-5p/HIF-1α pathway.
