The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 5: 676 - 682

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.05.009

Basic Research

Effect of pomegranate peel polyphenols on the malignant biological behavior of colon cancer cells by regulating the miR⁃138⁃5p/HIF⁃1α pathway

  • Hongyan BIAN ,
  • Shu ZHANG ,
  • Shanshan MENG ,
  • Ying WEI
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  • Department of Pathology，the First Affiliated Hospital of Henan University，Kaifeng 475000，Henan，China

Received date: 2024-11-20

  Online published: 2025-03-20

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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.

Key words： pomegranate peel polyphenols; miR-138-5p/HIF-1α pathway; colon cancer; proliferation; apoptosis; invasion; migration

Cite this article

Hongyan BIAN , Shu ZHANG , Shanshan MENG , Ying WEI . Effect of pomegranate peel polyphenols on the malignant biological behavior of colon cancer cells by regulating the miR⁃138⁃5p/HIF⁃1α pathway[J]. The Journal of Practical Medicine, 2025 , 41(5) : 676 -682 . DOI: 10.3969/j.issn.1006-5725.2025.05.009

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