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Epigenetic Changes of SOX17 in Lung Carcinoma and Functional Study

Author: YinDongTao
Tutor: LiuYang；GuoMingZhou
School: PLA Postgraduate Medical School
Course: Thoracic Surgery
Keywords: Lung cancer SOX17 Methylation Epigenetic
CLC: R734.2
Type: Master's thesis
Year: 2011
Downloads: 102
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Abstract

Background lung cancer led to the first cause of death worldwide, although there are a variety of treatment methods such as surgery, radiotherapy, chemotherapy and targeted therapy, but the overall 5-year survival rate is still very low. The incidence of lung cancer is a complicated process involving multiple genes of a multi-stage, genetics and epigenetic changes play an important role in its process. Epigenetics refers to, without changing the DNA sequence of the relevant gene and scientific impact of changes in gene expression in the cell division process. Down or missing caused by promoter region CpG island methylation of tumor suppressor gene expression is an important mechanism of epigenetic regulation, many studies have shown that this change played an important role in a variety of human malignant diseases. SOX17 is one of the members of the superfamily of SOX transcription factors, by 5'-(A / T) (A / T) CAA (A / T) G-3 'in combination with the target gene sequence, in embryonic development and the maintenance of the hematopoietic stem cells play a role. In recent years, multiple studies found, SOX17 Wnt signaling pathway by inhibiting the classic influence the occurrence and development of colon cancer, liver cancer, breast cancer and other types of human malignancies, and is considered a candidate tumor suppressor gene. SOX17 epigenetic changes in the lung and lung cancer relationship is no report, can become a candidate tumor suppressor gene of lung cancer is not clear. The purpose of detection SOX17 expression and methylation in lung cancer cell lines. 2. Detect SOX17 in the lung cancer and paracancerous organizations in the expression and methylation changes, analysis of clinical features. 3. Research SOX17 function in lung cancer cells and to explore the possible mechanism. 1 detected by RT-PCR and Westernblot cell lines SOX17 methyltransferase inhibitor 5-aza-dc treated (?) The nRNA and protein level of expression. 2 methylation-specific PCR (methylationspecificPCR, MSP) to detect the methylation status of the cell lines and tissue DNA SOX17. 3 immunohistochemical methods to detect the expression of SOX17 in lung cancer and corresponding adjacent noncancerous tissues. Liposomes transfected the SOX17 eukaryotic expression vector, G418 screening cells transiently transfected with SOX17. Colony formation affect the outcome of the Experimental Analysis of SOX17 lung cancer cell proliferation 1.SOX17 expression in lung cancer cell lines and alter the methylation the topics chosen four lung cancer cell lines: H23, A549, H446 and 95D. At the mRNA level, SOX17 in H23 expression, weak expression in A549 normal expression H446 and 95D; MSP test results show H23 in SOX17 methylation, A549, H446 and 95D partially methylated. 96 hours after 5-Aza-dC treatment, H23 restore expression, A549 upregulated, H446 and 95D expression did not change significantly. SOX17 the expression select two H23 and A549 cells detected at the protein level, the results show that the change consistent with the mRNA level. SOX17 gene expression levels in lung cancer cells by promoter methylation in regulation. 2.SOX17 expression and methylation in lung cancer tissues to change specimens of 83 cases of lung cancer, 53 cases of methylation (63.9%), and 31 cases of paraneoplastic specimens only five cases occurred methylation (16.1%) , next to cancer and cancer specimens methylation rate comparison, the difference was statistically significant (P lt; 0.05). 29 cancer and paraneoplastic tissue immunohistochemical staining results suggest that SOX17 expression in 25 cases of cancer tissue negative, 22 cases of methylation of the promoter region of the lung cancer cases were positive in only 1 methylated cases, the difference was statistically significant. Description methylation is an important mechanism for regulation of SOX17 expression. SOX17 methylation is associated with sex and degree of tumor differentiation, regardless of the tumor type, stage, and so on. 3. Recovery SOX17 expression in lung cancer cell proliferation colony formation experiments prompted recovery SOX17 expression in H23 cells, the number of cell clones significantly reduced, and the control group (empty vector transfected group) compared to the difference was statistically significant. Prompted SOX17 inhibit the proliferation of lung cancer cells. Conclusion SOX17 promoter methylation the predilection event in lung cancer, and SOX17 genes downregulated important mechanism; SOX17 methylation is associated with lung cancer patients' gender and degree of tumor differentiation; SOX17 inhibit the proliferation of lung cancer cells likely candidate as a lung tumor suppressor gene.

Epigenetic Changes of SOX17 in Lung Carcinoma and Functional Study

Abstract

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