Article

SOX17 methylation inhibits its antagonism of Wnt signaling pathway in lung cancer.

Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing 100853, China.
Discovery medicine (Impact Factor: 3.5). 07/2012; 14(74):33-40.
Source: PubMed

ABSTRACT The purpose of this study was to explore epigenetic changes and functions of SOX17 in human lung cancer. Five lung cancer cell lines and 88 primary lung cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), semi-quantitative reverse-transcription PCR, immunohistochemistry, luciferase reporter assays, colony-formation assays, and western blotting were used to analyze methylation changes and functions of SOX17 in lung cancer. SOX17 methylation was found in 60.2% of primary human lung cancer samples, and promoter region methylation of SOX17 silenced its expression. SOX17 methylation was associated with female patients and lung cancer differentiation. Colony-formation assays revealed that SOX17 suppressed lung cancer cell proliferation. Re-expression of SOX17 inhibited Wnt signaling in H23 lung cancer cell line. SOX17 acts as a Wnt signaling inhibitor.

0 Followers
 · 
117 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.
    International Journal of Molecular Sciences 12/2012; 13(12):15767-83. DOI:10.3390/ijms131215767 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of childhood chronic kidney disease (CKD). While mutations in several renal development genes have been identified as causes for CAKUT, most cases have not yet been linked to known mutations. Furthermore, the genotype-phenotype correlation is variable, suggesting that there might be additional factors that have an impact on the severity of CAKUT. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level, and are involved in many developmental processes. Although little is known about the function of specific miRNAs in kidney development, several have recently been shown to regulate the expression of, and/or are regulated by, crucial renal development genes present in other organ systems. In this review, we discuss how miRNA regulation of common developmental signaling pathways may be applicable to renal development. We focus on genes that are known to contribute to CAKUT in humans, for which miRNA interactions in other contexts have been identified, with miRNAs that are present in the kidney. We hypothesize that miRNA-mediated processes might play a role in kidney development through similar mechanisms, and speculate that genotypic variations in these small RNAs or their targets could be associated with CAKUT.
    Pediatric Nephrology 09/2013; 29(4). DOI:10.1007/s00467-013-2599-0 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To explore epigenetic regulation and the impact of chemokine CXCL14 on colorectal cancer, 7 colorectal cancer cell lines, 107 cases of primary colorectal cancer, and 10 cases of normal colorectal mucosa were evaluated in this study. Methylation specific PCR (MSP), semi-quantitative reverse-transcription PCR (RT-PCR), cell proliferation assay, colony formation, and transwell assay were performed for the evaluation. Complete methylation and loss of CXCL14 expression were found in 5 colorectal cancer cell lines. Partial methylation and weak expression were found in two cell lines. CXCL14 was methylated in 79.4% (85/107) of primary human colorectal cancer. No methylation was found in 10 cases of normal colorectal mucosa. Restoration of CXCL14 expression was induced by the 5-aza-2'-deoxycytidine (DAC) treatment. The cell viability was reduced and colony formation was inhibited by restoration of CXCL14 expression in HCT116 cells, a colorectal cancer cell line. The number of invasive and migration cells was reduced by CXCL14. The expression of MMP-2, Vimentin, and NF-κB was suppressed, and the expression of E-cadherin and IκB-α was induced by CXCL14. In conclusion, CXCL14 is frequently methylated in human colorectal cancer and promoter region hypermethylation silenced CXCL14 expression in colorectal cancer cells. Restoration of CXCL14 expression suppressed colorectal cancer proliferation. CXCL14 inhibits colorectal cancer migration, invasion, and epithelial-to-mesenchymal transition (EMT) by suppressing NF-κB signaling.
    Discovery medicine 10/2013; 16(88):137-147. · 3.50 Impact Factor