BMI1 induces malignant biological behavior in human oral squamous carcinoma cells via the NOTCH signaling pathway
10.19405/j.cnki.issn1000-1492.2024.12.008
- Author:
Yang Huang
1
,
2
;
Hong Ma
1
,
2
;
Hang Xiang
1
,
2
Author Information
1. Dept of Oral and Maxillofacial Surgery , Afiliated Stomatological Hospital of Guizhou Medical University , Guiyang 550004
2. School of Stomatology , Guizhou Medical University , Guiyang 550004
- Publication Type:Journal Article
- Keywords:
BMI1;
OSCC;
NOTCH;
cisplatin resistance;
proliferation;
invasion
- From:
Acta Universitatis Medicinalis Anhui
2024;59(12):2117-2126，2134
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate theBMI1-NOTCH signaling pathway that regulates proliferation, migration, invasion, apoptosis, and cisplatin(CDDP) sensitivity in human oral squamous cell carcinoma(OSCC) cells.
Methods:Human OSCC cell line CAL27 was used to construct the CAL27 cell line with lentivirus, which knocked down or overexpressedBMI1gene. The knockdown and control groups included: shBMI1-1, shBMI1-2, shBMI1-3, and shNC group, while the overexpression and control groups were BMI1 and NC group. RT-qPCR and Western blot were employed to verify transfection efficiency and select the cell group with the most effective knockdown. Western blot was used to detect the expression of NOTCH signaling pathway proteins, including NOTCH1, Delta-like ligand 1(DLL1), Jagged1(JAG1), and Hairy/enhancer-of-split 1(HES1), in the transformed CAL27 cells. Subsequently, the cells in each group were cultured with the drug solvents dimethyl sulfoxide(DMSO), CDDP, NOTCH pathway inhibitor gamma-secretase inhibitor(DAPT), and CDDP+DAPT, respectively, and the cell phenotype in each group were detected using CCK-8 assay, Wound healing assay, Transwell invasion assay, colony formation assay, and flow cytometry.
Results:Overexpression ofBMI1increased the expression levels of NOTCH pathway gene proteinsNOTCH1,DLL1,JAG1, andHES1(P<0.05). Under CDDP intervention, cells in the BMI1 group exhibited increased viability, invasion, migration, and colony formation abilities, and decreased apoptosis compared to the shBMI1 group(P<0.05). When comparing the CDDP group with the CDDP+DAPT group, the combination of medications resulted in a significant increase in the apoptosis rate and an increase in the sensitivity of cancer cells to CDDP(P<0.05).
Conclusion:BMI1may increase the cellular malignancy of CAL27 cell line by activating the NOTCH signaling pathway, promoting cell viability, migration, and invasion, as well as decreasing the cellular drug sensitivity to CDDP. Inhibition of the NOTCH pathway increases the cisplatin sensitivity of CAL27, and CDDP+DAPT has a synergistic cytotoxic effect to promote OSCC cell apoptosis.
- Full text:2025022715405097260BMI1经NOTCH信号通...口腔鳞癌细胞恶性生物学行为_黄炀.pdf
