Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX) Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal
A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.
Imoto I, Pimkhaokham A, Watanabe T, et al. Amplification and overexpression of TGIF2, a novel homeobox gene of the TALE superclass, in ovarian cancer cell lines. Biochem Biophys Res Commun 2000;276(1):264-70.
Hu Y, Yu H, Shaw G, et al. Differential roles of TGIF family genes in mammalian reproduction. BMC Dev Biol 2011;11:58.
Holland PW, Booth HA, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol 2007;5:47.
Reza Raoofian, Mohammad Reza Noori-Daloii, Samira Saee-Rad, et al. Differential expression of human homeodomain TGIFLX in brain tumor cell lines. Acta Med Iran 2013;51(12):834-41.
Bertolino E, Reimund B, Wildt-Perinic D, et al. A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif. J Bioll Chem 1995;270(52):31178-88.
Melhuish TA, Gallo CM, Wotton D. TGIF2 interacts with histone deacetylase 1 and represses transcription. J Biol Chem 2001;276(34):32109-14.
Powers SE, Taniguchi K, Yen W, et al. Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development 2010;137(2):249-59.
Burglin TR. Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals. Nucleic Acids Res 1997;25(21):4173-80.
Hyman CA, Bartholin L, Newfeld SJ, et al. Drosophila TGIF proteins are transcriptional activators. Mol Cell Biol 2003;23(24):9262-74.
Wang Y, Wang L, Wang Z. Transgenic analyzes of TGIF family proteins in Drosophila imply their role in cell growth. JGenet Genomics2008;35(8):457-65.
Yu YY, Pan YS, Zhu ZG. Homeobox genes and their functions on development and neoplasm in gastrointestinal tract. Eur JSurg Oncol 2007;33(2):129-32.
Blanco-Arias P, Sargent CA, Affara NA. The humanspecific Yp11.2/Xq21.3 homology block encodes a potentially functional testis-specific TGIF-like retroposon. Mamm Genome 2002;13(8):463-8.
Ousati Ashtiani Z, Ayati M, Modarresi MH, et al. Association of TGIFLX/Y mRNA expression with prostate cancer. Med Oncol 2009;26(1):73-7.
Aarabi M, Ousati-Ashtiani Z, Nazarian A, et al. Association of TGIFLX/Y mRNA expression with azoospermia in infertile men. Mol Reprod Devn2008;75(12):1761-6.
Raoofian R, Noori-Daloii MR, Saee-Rad S, et al. Differential expression of human homeodomain TGIFLX in brain tumor cell lines. Acta Med Iran 2013;51(12):834-41.
Akbari A, Amanpour S, Muhammadnejad S, et al. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma. Daru 2014;22:47
Akbari A, Ghahremani MH, Mobini GR, et al. Downregulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208). Iran J Basic Med Sci 2015;18(9):856-61.
Saffari M, Dinehkabodi OS, Ghaffari SH, et al. Identification of novel p53 target genes by cDNA AFLP in glioblastoma cells. Cancer Lett 2009;273(2):316-22.
Elham Kazemi-Rad MM, Mohammad Bagher Khadem- Erfan, Mojtaba Saffari,et al. Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach. Exp Parasitol 2013;135(2):344-9.
Bagher Khadem Erfan M, Mohebali M2, Kazemi-Rad E, et al. Downregulation of Calcineurin Gene Is Associated with Glucantime Resiatance in Leishmania infantum. Iran J Parasitol 2013;8(3):359-66.
Bassam BJ, Caetano-Anolles G, Gresshoff PM. Fast and sensitive silver staining of DNA in polyacrylamide gels. Anal Biochem 1991;196(1):80-3.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25(4):402-8.
Akbari A, Mobini GR, Maghsoudi R, et al. Modulation of transforming growth factor-β signaling transducers in colon adenocarcinoma cells induced by staphylococcal enterotoxin B. Mol Med Rep 2016;13(1):909-91.
Altschul SF, Madden TL, Schaffer AA, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nuclic Acids Res 1997;25(17):3389-402.
Shen A, Chen H, Chen Y, et al. Pien Tze Huang Overcomes Multidrug Resistance and Epithelial- Mesenchymal Transition in Human Colorectal Carcinoma Cells via Suppression of TGF-beta Pathway. Evid BasedComplement Alternat Med2014;2014:679436.
Yang J, Fu M, Ding Y, et al. High SHIP2 Expression Indicates Poor Survival in Colorectal Cancer. Dis Markers 2014;2014:218968.
Krohn S, Garin A, Gabay C, et al. The Activity of CCL18 is Principally Mediated through Interaction withGlycosaminoglycans. Front Immunol 2013;4:193.
Lev S. Molecular aspects of retinal degenerative diseases. Cell Mol Neurobiol 2001;21(6):575-89.
Ocaka L, Spalluto C, Wilson DI, et al. Chromosomallocalization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3.Cytogenet Genome Res 2005;108(4):293-302.
Lev S, Hernandez J, Martinez R, et al. Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein. Mol Cell Biol 1999;19(3):2278-88.
Tian D, Litvak V, Toledo-Rodriguez M, et al. Nir2, a novel regulator of cell morphogenesis. Mol Cell Biol 2002;22(8):2650-62.
Litvak V, Tian D, Carmon S, et al. Nir2, a human homolog of Drosophila melanogaster retinal degeneration B protein, is essential for cytokinesis. Mol Cell Biol 2002;22(14):5064-75.
Chen J, Yao Y, Gong C, et al. CCL18 from tumorassociated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell 2011;19(4):541-55.
Leung SY, Yuen ST, Chu KM, et al. Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer. Gastroenterology2004;127(2):457-69.
Tian D, Lev S. Cellular and developmental distribution of human homologues of the Drosophilia rdgB protein in the rat retina. Invest Ophthalmol Vis Sci 2002;43(6):1946-53.
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