Alteration of DACH1 methylation patterns in lung cancer contributes to cell proliferation and migration.

Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of total lung cancer cases. Dachshund homolog 1 (DACH1), is a protein encoded by the DACH1 gene in humans. DACH1 inhibits lung adenocarcinoma invasion and tumor growth but has a lower expression in NSCLC. To investigate the mechanisms of decreased DACH1 expression, its DNA methylation patterns were investigated. The results showed a higher methylation rate in NSCLC compared with the adjacent normal lung tissues. Cell transfection experiments showed that increased methylation impaired transcription factor transactivation. In vivo demethylation treatment and overexpression of DACH1 increased apoptosis and decreased migration and invasion in NSCLC A549 cells. Our research provides new insight into NSCLC pathogenesis and identifies a new therapeutic target.

[1]  C. Croce,et al.  Retraction Note: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. , 2022, Nature medicine.

[2]  F. López-Ríos,et al.  Biological therapies in nonsmall cell lung cancer , 2017, European Respiratory Journal.

[3]  Kuen-Feng Chen,et al.  EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cells. , 2017, European journal of cancer.

[4]  C. Zappa,et al.  Non-small cell lung cancer: current treatment and future advances. , 2016, Translational lung cancer research.

[5]  R. Pestell,et al.  The retinal determination gene network: from developmental regulator to cancer therapeutic target , 2016, Oncotarget.

[6]  Kongming Wu,et al.  The DACH/EYA/SIX gene network and its role in tumor initiation and progression , 2016, International journal of cancer.

[7]  Huafei Li,et al.  DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3 , 2016, Tumor Biology.

[8]  R. Pestell,et al.  Endogenous Dach1 in cancer , 2015, Oncoscience.

[9]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[10]  Hua Wu,et al.  DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling , 2015, Oncotarget.

[11]  Hua Wu,et al.  DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells , 2014, Journal of Hematology & Oncology.

[12]  Huiqing Yuan,et al.  Differential regulation of MMPs by E2F1, Sp1 and NF-kappa B controls the small cell lung cancer invasive phenotype , 2014, BMC Cancer.

[13]  J. Herman,et al.  Epigenetic regulation of DACH1, a novel Wnt signaling component in colorectal cancer , 2013, Epigenetics.

[14]  H. Rui,et al.  Dachshund binds p53 to block the growth of lung adenocarcinoma cells. , 2013, Cancer research.

[15]  B. Bergman,et al.  Health related quality of life in locally advanced NSCLC treated with high dose radiotherapy and concurrent chemotherapy or cetuximab--pooled results from two prospective clinical trials. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  Andres Metspalu,et al.  Methylation Markers of Early-Stage Non-Small Cell Lung Cancer , 2012, PloS one.

[17]  J. Sun,et al.  EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers , 2011, Nature Medicine.

[18]  M. Lisanti,et al.  Altered expression of DACH1 and cyclin D1 in endometrial cancer , 2009, Cancer biology & therapy.

[19]  H. Rui,et al.  The cell fate determination factor DACH1 is expressed in estrogen receptor-alpha-positive breast cancer and represses estrogen receptor-alpha signaling. , 2009, Cancer research.

[20]  Sung-Liang Yu,et al.  MicroRNA signature predicts survival and relapse in lung cancer. , 2008, Cancer cell.

[21]  Wen-li Ma,et al.  Analysis of SOX4 gene mutation in non-small cell lung cancer tissues. , 2007, Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.

[22]  D. Lane,et al.  Nutlin-3 inhibits the NFκB Pathway in a p53 Dependent Manner: Implications in Lung Cancer Therapy , 2007, Cell cycle.

[23]  Ales Cvekl,et al.  DACH1 Is a Cell Fate Determination Factor That Inhibits Cyclin D1 and Breast Tumor Growth , 2006, Molecular and Cellular Biology.

[24]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[25]  S. L. Wong,et al.  Towards a proteome-scale map of the human protein–protein interaction network , 2005, Nature.

[26]  V. Ambros The functions of animal microRNAs , 2004, Nature.

[27]  R. Stupp,et al.  Small cell lung cancer: state of the art and future perspectives. , 2004, Lung cancer.

[28]  Kamel Jabbari,et al.  Cytosine methylation and CpG, TpG (CpA) and TpA frequencies. , 2004, Gene.

[29]  Anping Li,et al.  DACH1 Inhibits Transforming Growth Factor-β Signaling through Binding Smad4* , 2003, Journal of Biological Chemistry.

[30]  Daisuke Hattori,et al.  DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation , 2003, Science.

[31]  S. Krauss,et al.  Targeted disruption of mouse Dach1 results in postnatal lethality , 2003, Developmental dynamics : an official publication of the American Association of Anatomists.

[32]  Robert Brown,et al.  Epigenomics and epigenetic therapy of cancer. , 2002, Trends in molecular medicine.

[33]  K Takahashi,et al.  DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue. , 2001, Genomics.

[34]  T. Bestor,et al.  The DNA methyltransferases of mammals. , 2000, Human molecular genetics.

[35]  S. Benzer,et al.  Multiple roles of the eyes absent gene in Drosophila. , 1998, Developmental biology.

[36]  H. Cedar DNA methylation and gene activity , 1988, Cell.

[37]  S. Aaronson,et al.  In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. , 1973, Journal of the National Cancer Institute.

[38]  J. Davie,et al.  Protein arginine methyltransferases (PRMTs): role in chromatin organization. , 2015, Advances in biological regulation.

[39]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[40]  Anping Li,et al.  DACH1 inhibits transforming growth factor-beta signaling through binding Smad4. , 2003, The Journal of biological chemistry.