Inhibiting miR-155-5p promotes proliferation of human submandibular gland epithelial cells in primary Sjogren's syndrome by negatively regulating the PI3K/AKT signaling pathway via PIK3R1.
10.12122/j.issn.1673-4254.2025.01.09
- Author:
Yuru ZHANG
1
;
Lei WAN
1
;
Haoxiang FANG
2
;
Fangze LI
1
;
Liwen WANG
1
;
Kefei LI
1
;
Peiwen YAN
1
;
Hui JIANG
1
Author Information
1. First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
2. College of Traditional Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
- Publication Type:Journal Article
- Keywords:
PI3K/AKT signaling pathway;
PIK3R1;
inflammatory factors;
miR-155-5p;
primary Sjogren's syndrome
- MeSH:
Humans;
MicroRNAs/genetics*;
Cell Proliferation;
Signal Transduction;
Proto-Oncogene Proteins c-akt/metabolism*;
Sjogren's Syndrome/pathology*;
Epithelial Cells/cytology*;
Submandibular Gland/cytology*;
Phosphatidylinositol 3-Kinases/metabolism*;
Apoptosis;
Class Ia Phosphatidylinositol 3-Kinase;
Cells, Cultured
- From:
Journal of Southern Medical University
2025;45(1):65-71
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS).
METHODS:Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway.
RESULTS:Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression.
CONCLUSIONS:In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
