miR-195 regulates FOXK1 gene and inhibits PI3K/Akt pathway’s biological behavior in stomach adenocarcinoma
10.3760/cma.j.cn.115807-20220114-00017
- VernacularTitle:miR-195调控FOXK1基因抑制PI3K/Akt通路对胃癌细胞生物学行为的机制研究
- Author:
Xiaobin FAN
1
;
Fengfeng SONG
;
Xiaoqing LI
;
Wenxing LI
;
Xianying FAN
;
Yanwei HU
;
Zhigang SONG
;
Qiang WANG
;
Yanjun LIAN
Author Information
1. 邢台市第三医院胃肠外科，邢台 054099
- Keywords:
Stomach adenocarcinoma;
miR-195;
FOXK1;
PI3K/Akt;
Biological characteristics;
Regulation mechanism
- From:
Chinese Journal of Endocrine Surgery
2022;16(6):655-661
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.
