Chang Li1, Jun Chen, Tengfei Chen, Zhenlei Xu, Chun Xu, Cheng Ding, Yuxuan Wang, Zhe Lei, Hong-Tao Zhang, Jun Zhao. 1. Department of Thoracic and Cardiovascular Surgery (CL, JC, TC, ZX, CX, CD, YW, JZ), the First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China; Soochow University Laboratory of Cancer Molecular Genetics (CL, ZL, H-TZ, JZ), Medical College of Soochow University, Suzhou, China; and Suzhou Key Laboratory for Cancer Molecular Genetics (CL, ZL, H-TZ, JZ), Suzhou, China.
Abstract
BACKGROUND: Lung cancer is now the leading cause of malignant tumor-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Human Disabled-2 (DAB2) was reported to act as a tumor suppressor gene and was found downregulated in numerous cancer types. However, the expression of DAB2 in NSCLC and the mechanism of DAB2 expression regulation remain unclear. METHODS: DAB2 expression was analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blot in 20 paired primary NSCLC tissues and corresponding normal lung tissues. Immunohistochemistry assay was performed in paired NSCLC tissues from another 20 patients. Methylation status of DAB2 promoter was analyzed using bisulfite sequencing polymerase chain reaction. RESULTS: DAB2 messenger RNA level was significantly lower in NSCLC tissues than normal tissues in 95.0% of the group of patients under investigation. In addition, NSCLC tissues showed a significant reduction in DAB2 protein when compared with normal tissues. Importantly, 85% of NSCLC tissues (17/20) had high methylation in DAB2 promoter when compared with normal tissues. CONCLUSIONS: DAB2 expression is decreased in NSCLC, and the frequent methylation event at sites -86 to 226 of the DAB2 gene could contribute to the downregulation of DAB2.
BACKGROUND:Lung cancer is now the leading cause of malignant tumor-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. HumanDisabled-2 (DAB2) was reported to act as a tumor suppressor gene and was found downregulated in numerous cancer types. However, the expression of DAB2 in NSCLC and the mechanism of DAB2 expression regulation remain unclear. METHODS:DAB2 expression was analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blot in 20 paired primary NSCLC tissues and corresponding normal lung tissues. Immunohistochemistry assay was performed in paired NSCLC tissues from another 20 patients. Methylation status of DAB2 promoter was analyzed using bisulfite sequencing polymerase chain reaction. RESULTS:DAB2 messenger RNA level was significantly lower in NSCLC tissues than normal tissues in 95.0% of the group of patients under investigation. In addition, NSCLC tissues showed a significant reduction in DAB2 protein when compared with normal tissues. Importantly, 85% of NSCLC tissues (17/20) had high methylation in DAB2 promoter when compared with normal tissues. CONCLUSIONS:DAB2 expression is decreased in NSCLC, and the frequent methylation event at sites -86 to 226 of the DAB2 gene could contribute to the downregulation of DAB2.
Authors: Vanessa Figliuolo da Paz; Deepa R Jamwal; Michael Gurney; Monica Midura-Kiela; Christy A Harrison; Christopher Cox; Jean M Wilson; Fayez K Ghishan; Pawel R Kiela Journal: Front Immunol Date: 2019-02-27 Impact factor: 7.561