Cancer Management and Research (Jun 2020)
CFTR Functions as a Tumor Suppressor and Is Regulated by DNA Methylation in Colorectal Cancer
Abstract
Can Liu,1 Chao Song,2 Jiaxi Li,3 Qing Sun1,3 1Department of Pathology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Department of Pathology, Zibo Central Hospital, Zibo, Shandong Province, People’s Republic of China; 3Department of Pathology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Qing SunDepartment of Pathology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jingshi Street, Jinan 250014, Shandong Province, People’s Republic of ChinaTel +86-531-89269710Email [email protected]: Cystic fibrosis transmembrane conductance regulator (CFTR) was shown to be downregulated or silenced in carcinomas and acts as a candidate tumor suppressor gene. However, the function of CFTR gene in colorectal cancer (CRC) is still unclear. This aim of this study was to investigate the CFTR promoter methylation status and its impact on the expression and functional role of CFTR in CRC development.Patients and Methods: CFTR expression in CRC tissues and CRC cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The promoter methylation status of CFTR was measured using methylation-specific PCR (MSP). colony formation, transwell, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate the effect of CFTR overexpression in CRC cell lines.Results: qRT-PCR and IHC results indicated that CFTR expression was downregulated in the CRC tissues compared to the adjacent normal tissues. The promoter methylation status of CFTR was further analyzed in 70 CRC specimens. MSP validation showed methylation of CFTR promoter in 62.2% (45/70) of CRC tissues. The methylation of CFTR promoter was significantly associated with age (P=0.013) and lymph node metastasis (P=0.026) in CRC tissues. Results of transwell, MTT, and colony formation assays showed that CFTR overexpression inhibited the migration, invasion, and proliferation of CRC cells.Conclusion: CFTR expression was downregulated in CRC and promoter methylation may be responsible for this downregulation. Overexpression of CFTR may suppress CRC tumor growth by inhibiting the proliferation, migration, and invasion of CRC cells. CFTR promoter methylation was significantly correlated with lymph node metastasis; thus, CFTR may be a potential marker for lymph node metastasis of CRC.Keywords: CFTR, DNA methylation, colorectal cancer, lymph node metastasis
