Effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration of laryngeal squamous cell carcinoma.
- Author:
Lin-lin YUAN
1
;
Feng WANG
;
Sheng-lei LI
;
Wei-hua LOU
;
Liu-xing WANG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Cadherins; metabolism; Carcinoma, Squamous Cell; genetics; metabolism; pathology; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin D1; metabolism; Cyclin E; metabolism; Cyclin-Dependent Kinase 2; metabolism; Down-Regulation; Female; Histone Deacetylase 6; Histone Deacetylases; genetics; metabolism; Humans; Laryngeal Neoplasms; genetics; metabolism; pathology; Lymphatic Metastasis; Male; Matrix Metalloproteinase 9; metabolism; Middle Aged; Neoplasm Staging; Oncogene Proteins; metabolism; Proto-Oncogene Proteins p21(ras); metabolism; RNA, Small Interfering; genetics; Transfection
- From: Chinese Journal of Oncology 2012;34(6):430-435
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo detect the expression of histone deacetylase 6 (HDAC6) in laryngeal squamous cell carcinoma, and to analyze the effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration of laryngeal squamous cell carcinoma cell line Hep-2 cells, and to explore their possible molecular mechanisms.
METHODSImmunohistochemistry was used to detect the expression of HDAC6 protein in 55 cases of laryngeal squamous cell carcinoma and 20 cases of normal laryngeal mucosa. HDAC6 siRNA and control siRNA were transfected into Hep-2 cells via lipofectamine 2000, and the interfering effect was analyzed using Western blotting. The effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and Boyden chamber, respectively. Finally, Western blotting was used to detect the expressions of cell cycle, proliferation and migration related proteins.
RESULTSThere was a high level expression of HDAC6 protein in laryngeal squamous cell carcinoma, and its expression was not related to age and sex of the patients (P > 0.05), but closely associated with the degree of histological differentiation, TNM staging and lymph node metastasis (P < 0.05). HDAC6 siRNA effectively down-regulated the expression of HDAC6 protein in laryngeal squamous cell carcinoma cell line Hep-2 cells, and downregulation of its expression obviously inhibited cell proliferation, arrested cell cycle at G(0)/G(1) phase and decreased cell migration ability in Hep-2 cells. Additionally, the downregulation of HDAC6 protein expression markedly decreased the expressions of cyclin D1, cyclin E, cdk2 and MMP-9 proteins, but increased the expressions of p21 and E-cadherin proteins.
CONCLUSIONSHDAC6 may play a pivotal role in the carcinogenesis and development of laryngeal squamous cell carcinoma. The downregulation of HDAC6 expression-mediated cell proliferation inhibition, cell cycle arrest and decreased cell migration ability may be closely associated with the decrease of cyclin D1, cyclin E, cdk2 and MMP-9 proteins and increase of p21 and E-cadherin proteins.
