Araştırma Makalesi
Yıl 2019,
Cilt: 5 Sayı: 2, 106 - 119, 28.08.2019
Öz
Objectives: The objective of this study is to define novel biomarkers for gastric neoplasm (GN) via in silico analysis that takes GN-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing T-UCR among them and potentiates their relevance with GN. Based on this study we can plan new in vitro and in vivo studies.
Methods: Four miRNAs of which clinical relevances with GN were
proved experimentally were exported via mirTarbase. Using the ComiR database,
1008 genes targeted by these 4 miRNAs simultaneously were identified. Genes
containing T-UCR and showing potential ceRNA activity were extracted. Among
GN-associated ceRNAs including T-UCR, we identified genes with significant
expression differences between GN and normal stomach tissue using the GEPIA
database. The statistical evaluation of the association of NFAT5 and CLK3 genes with
GN was performed by Spearman correlation test in GEPIA database.
Results:
GN-associated ceRNAs cross-matching with genes including T-UCR in their exonic
regions were NFAT5 and CLK3. We identified genes with significant expression differences between
GN and normal stomach tissues among GN-associated ceRNAs including T-UCR.
According to this analysis, only NFAT5 gene
was significantly higher expressed in GN than in normal stomach tissue while
the other didn’t show any significant differential expression pattern. NFAT5 and CLK3 genes were found to be significantly correlated with GN
(p<0.001; R=0.22)
Conclusion:
All in all, this is the study associating NFAT5
gene with GN for the first time and giving it ongogenic potential for GN.
Still, larger and more comprehensive studies are needed on this issue.
Anahtar Kelimeler
Kaynakça
- Amara S, Alotaibi D, Tiriveedhi V. NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells. Oncol Lett. 2016; 12(2):933-43.
- Bejerano G, Pheasant M, Makunin I. Ultraconserved Elements in the Human Genome. Science. 2004; 304(5675), pp. 1321-1325
- Calin GA, Dumitru CD, Shimizu M. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci. 2002; 99(24):15524-9.
- Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005; 65:6029
- Cheung CY, Ko BC. NFAT5 in cellular adaptation to hypertonic stress–regulations and functional significance. J Mol Signal. 2013; 8(1):5.
- Chen M, Sastry SK, O'Connor KL. Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells. Am J Physiol-Cell Ph. 2011; 300(5):C1155-C63.
- Chou CH, Shrestha S, Yang, CD. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions Nucleic Acids Research, 2018; 46 (D1), D296–D302,
- Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic acids research. 2013; 41(W1), W159-W164.
- Fassan M, Dall'Olmo L, Galasso M, Braconi C, Pizzi M, Realdon S, Volinia S, Valeri N ,Gasparini P, Baffa R, Souza RF, Vicentini C, D'Angelo E, Bornschein J, Transcribed ultraconserved noncoding RNAs (TUCR)are involved in Barrett's esophaguscarcinogenesis.Onco Target.2014: 30;5(16):7162-71.
- Guo K, Jin F. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression. Biochem Bioph Res Co. 2015; 465(3):644-9.
- He H, Jazdzewski K, Li W, Liyanorachchi S, Nagy R, Volinia S. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 2005; 102:19075-80.
- Iorio MV, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S. MicroRNA gene expression deregulation in human breast cancer. Cancer Research 2005; 65:7065-70.
- Kim YK, Yeo J, Ha M. Cell adhesion- dependent control of microRNA decay. Molecular Cell 2011; 43:1005-14.
- Kuper C, Beck F-X, Neuhofer W. NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells. Front Physiol. 2014; 5:293
- Lamy P, Andersen CL, Dyrskjøt L, Tørring N, Ørntoft T, Wiuf C. Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006; 95 (10): 1415-18
- Metzler M, Wilda M, Busch K. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. 2004; 39:167-9.
- Michael MZ, O.Connor SM, van Holst Pellekaan NG. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003; 1:882-91.
- Pan H.W, Li S.C, Tsai K.W. MicroRNA Dysregulation in Gastric Cancer, Current Pharmaceutical Design, 2013; 19(7):1273-84.
- Qi X, Zhang D.H, Wu N, Xiao J.H, Wang X, Ma W. CeRNA in cancer: possible functions and clinical implications. J Med Genet 2015; 0:1–9. doi:10.1136/jmedgenet-2015-103334.
- Sevignani C, Calin GA, Siracusa LD. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome. 2006; 17(3):189-202.
- Sevli S, Uzumcu A, Solak M, Ittman M, Ozen M. The function microRNAs, small potent molecules in human prostate cancer. Prostate Cancer P D 2010; 13:208-17.
- Schiller MP, Wilkerson PM. Gastric neoplasms. Surgery. 2017: 35:(11): 635-643
- Tang Z, Li C, Kang B. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic acids research. 2017; 45(W1), W98-W102.
- Zhou YM, Chen LJ, Barlogie B. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 7904-9.
Yıl 2019,
Cilt: 5 Sayı: 2, 106 - 119, 28.08.2019
Öz
Kaynakça
- Amara S, Alotaibi D, Tiriveedhi V. NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells. Oncol Lett. 2016; 12(2):933-43.
- Bejerano G, Pheasant M, Makunin I. Ultraconserved Elements in the Human Genome. Science. 2004; 304(5675), pp. 1321-1325
- Calin GA, Dumitru CD, Shimizu M. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci. 2002; 99(24):15524-9.
- Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005; 65:6029
- Cheung CY, Ko BC. NFAT5 in cellular adaptation to hypertonic stress–regulations and functional significance. J Mol Signal. 2013; 8(1):5.
- Chen M, Sastry SK, O'Connor KL. Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells. Am J Physiol-Cell Ph. 2011; 300(5):C1155-C63.
- Chou CH, Shrestha S, Yang, CD. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions Nucleic Acids Research, 2018; 46 (D1), D296–D302,
- Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic acids research. 2013; 41(W1), W159-W164.
- Fassan M, Dall'Olmo L, Galasso M, Braconi C, Pizzi M, Realdon S, Volinia S, Valeri N ,Gasparini P, Baffa R, Souza RF, Vicentini C, D'Angelo E, Bornschein J, Transcribed ultraconserved noncoding RNAs (TUCR)are involved in Barrett's esophaguscarcinogenesis.Onco Target.2014: 30;5(16):7162-71.
- Guo K, Jin F. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression. Biochem Bioph Res Co. 2015; 465(3):644-9.
- He H, Jazdzewski K, Li W, Liyanorachchi S, Nagy R, Volinia S. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 2005; 102:19075-80.
- Iorio MV, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S. MicroRNA gene expression deregulation in human breast cancer. Cancer Research 2005; 65:7065-70.
- Kim YK, Yeo J, Ha M. Cell adhesion- dependent control of microRNA decay. Molecular Cell 2011; 43:1005-14.
- Kuper C, Beck F-X, Neuhofer W. NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells. Front Physiol. 2014; 5:293
- Lamy P, Andersen CL, Dyrskjøt L, Tørring N, Ørntoft T, Wiuf C. Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006; 95 (10): 1415-18
- Metzler M, Wilda M, Busch K. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. 2004; 39:167-9.
- Michael MZ, O.Connor SM, van Holst Pellekaan NG. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003; 1:882-91.
- Pan H.W, Li S.C, Tsai K.W. MicroRNA Dysregulation in Gastric Cancer, Current Pharmaceutical Design, 2013; 19(7):1273-84.
- Qi X, Zhang D.H, Wu N, Xiao J.H, Wang X, Ma W. CeRNA in cancer: possible functions and clinical implications. J Med Genet 2015; 0:1–9. doi:10.1136/jmedgenet-2015-103334.
- Sevignani C, Calin GA, Siracusa LD. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome. 2006; 17(3):189-202.
- Sevli S, Uzumcu A, Solak M, Ittman M, Ozen M. The function microRNAs, small potent molecules in human prostate cancer. Prostate Cancer P D 2010; 13:208-17.
- Schiller MP, Wilkerson PM. Gastric neoplasms. Surgery. 2017: 35:(11): 635-643
- Tang Z, Li C, Kang B. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic acids research. 2017; 45(W1), W98-W102.
- Zhou YM, Chen LJ, Barlogie B. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 7904-9.
Toplam 24 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 28 Ağustos 2019 |
| Yayımlandığı Sayı | Yıl 2019 Cilt: 5 Sayı: 2 |
