MiR203 Lost Suppressor Genes Function in the Process of Barrett’s Esophagus Carcinogenesis Because of High Methylation in Promoter
Clinical Medicine Research
Volume 8, Issue 1, January 2019, Pages: 21-26
Received: Nov. 13, 2018;
Accepted: Jan. 11, 2019;
Published: Apr. 1, 2019
Views 101 Downloads 15
Liu Tianyu, Department of Digestion and Gastroenterology, Suining Central Hospital Affiliated to Chongqing Medical University, Suining, China
Long Xiaoqi, Department of Digestion and Gastroenterology, Suining Central Hospital Affiliated to Chongqing Medical University, Suining, China
This study was designed to explore the role of MiR203 promoter methylation in the process of Barrett’s esophagus carcinogenesis. RT-PCR was used to detect the expression levels of miRNA-203 in Barrett’s esophagus, esophageal cancer and normal esophageal mucosa cell lines, before and after the treatment of demethylation. MiR203 promoter methylation levels in these cell lines were measured by Methylation Specific PCR (MSP). Immunohistochemistry was used to test the expression and distribution of K-Ras, a target of miR203, in esophageal cancer, BE and normal esophagus tissues. The following results were found based on the above methods. MiR203 expression levels were reduced obviously in Barrett esophagus and esophageal cancer cells than normal esophageal cells, the difference was statistically significant (P=0.003). After demethylation treatment, miR203 expression levels were significantly increased in Barrett's esophagus and esophageal cancer cells, the differences were statistically significant (P=0.03). MSP results showed that miR203 promoter changed to be low-methylation or non-methylation after demethylation treatment. In conclusion, MiR203 in Barrett's esophagus and esophageal cancer cells reduced expression is related to its Promoter methylation, miR203 promoter methylation throughout the carcinogenesis of Barrett's esophagus, it may become a key molecular biomarker in process of Barrett esophagus cancerous, and may become the prevention and treatment targets of Barrett esophagus carcinogenesis.
MiR203 Lost Suppressor Genes Function in the Process of Barrett’s Esophagus Carcinogenesis Because of High Methylation in Promoter, Clinical Medicine Research.
Vol. 8, No. 1,
2019, pp. 21-26.
Feber A, Xi L, Luketich J D, et a1. MicroRNA expression profiles of esophageal cancer [J]. Thorac Cardiovasc Surg, 2008, 135 (2):255-260.
Szigeti KA, Galamb O, Kalmár A, et al. Role and alterations of DNA methylation during the aging and cancer [J]. Orv Hetil. 2018, 159 (1):3-15.
Rahertson KD. DNA methylation and human disease [J]. Nat RevGe net, 2005, 6 (8):597-610.
Lü L, Liu T, Gao J, et al. Aberrant methylation of microRNA-193b in human Barrett's esophagus and esophageal adenocarcinoma [J]. Mol Med Rep. 2016, 14 (1):283-8.
Belghazi K1, van Vilsteren FGI1, Weusten BLAM2, et a1. Long-term follow-up results of stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia [J]. Gastrointest Endosc, 2017, 4 (25): 31820-318255.
Zhang W, Wang DH. Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? [J]. Dig Dis Sci. 2018, 63 (8):2005-2012.
Rajendra S, Sharma P. Barrett Esophagus and Intramucosal Esophageal Adenocarcinoma [J]. Hematol Oncol Clin North Am. 2017 31 (3):409-426.
Noguchi S, Mori T, Nakagawa T, et a1. DNA methylation contributes toward silencing of antioncogenic microRNA-203 in human and canine melanoma cells [J]. Melanoma Res. 2015, 25 (5):390-398.
Yang J, Wang S, Wang F, et a1. Downregulation of miR-10b promotes osteoblast differentiation through targeting Bcl6 [J]. Int J Mol Med. 2017, 39 (6):1605-1612.
Trohatou O, Zagoura D, Orfanos NK, et a1. miR-26a mediates adipogenesis of amniotic fluid mesenchymal stem/stromal cells via PTEN, Cyclin E1, and CDK6 [J]. Stem Cells Dev. 2017, 26 (7):482-494.
Liu F, Chen N, Xiao R, et a1. MiR-144-3p serves as a tumor suppressor for renal cell carcinoma and inhibits its invasion and metastasis by targeting MAP3K8. Biochem Biophys Res Commun [J]. 2016, 480 (1):87-93.
Hao Q, Lu X, Liu N, et al. Posttranscriptional deregulation of Src due to aberrant miR34a and miR203 contributes to gastric cancer development [J]. BMB Rep. 2013, 46 (6):316-21.
Xu D, Wang Q, An Y, et al. MiR-203 regulates the proliferation, apoptosis and cell cycle progression of pancreatic cancer cells by targeting Surviving [J]. Mol Med Rep. 2013; 8 (2):379-84.
DeCastro AJ, Dunphy KA, Hutchinson J, et al. MiR203 mediates subversion of stem cell properties during mammary epithelial differentiation via repression of ΔNP63αand promotes mesenchymal-to-epithelial transition [J]. Cell Death Dis. 2013 28; 4:e514.
Wong KY, Liang R, So CC, et al. Epigenetic silencing of MIR203 in multiple myeloma [J]. Br J Haematol. 2011; 154 (5):569-78.
Qu H, Xu W, Huang Y, Yang S, et al. Circulating miRNAs: Promising Biomarkers of Human Cancer [J]. Asian Pacific journal of cancer prevention: APJCP 2011, 12 (5):1117-25.
Lee S, Jung JW, Park SB, et al. Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging [J].. Cell Mol Life Sci. 2011 Jan; 68 (2):325-36.
Nussinov R, Wang G, Tsai CJ, et al. Calmodulin and PI3K Signaling in KRAS Cancers [J]. Trends Cancer. 2017, 3 (3):214-224.
Markman B, Javier Ramos F, Capdevila J, et al. EGFR and KRAS in colorectal cancer [J]. Adv Clin Chem, 2010; 51:71-119.
Sug Hyung Lee, Jong Woo Lee, et al. Young Hwa Soung, et al. BRAF and KRAS mutations in stomach cancer [J]. Oncogene 2003, 22, 6942–6945.
S. Stremitzer, J. Stift, B. Gruenberger, et al. KRAS status and outcome of liver resection after neoadjuvant chemotherapy including bevacizumab [J]. British Journal of Surgery, 2012, 99 (11), 1575–1582.
Nakano H, Yamada Y, Miyazawa T, et al. Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells [J]. Int J Oncol. 2013, 42 (6):1875-82.