American Journal of Clinical and Experimental Medicine
Volume 7, Issue 1, January 2019, Pages: 1-6
Received: Jan. 17, 2019;
Published: Feb. 1, 2019
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Tingting Chen, Department of Gastroenterology, Binzhou People's Hospital, Binzhou City, P. R. China
Hongna Lv, Department of Gastroenterology, Binzhou People's Hospital, Binzhou City, P. R. China
Yanping Xu, Department of Gastroenterology, Binzhou People's Hospital, Binzhou City, P. R. China
Wenjing Du, Technical Office, Binzhou Intermediate People's Court, Binzhou City, P. R. China
Rui Zhang, Technical Office, People's Court of Bincheng District, Binzhou City, P. R. China
The aim of this paper is to study the mechanism of MLH1 gene expression and regulation in colorectal cancer, and to clarify the impact of 5' end CpG island aberrant methylation on the regulation of MLH1 gene expression. RT-PCR assay was used to detect the expression of MLH1 gene mRNA in 10 colon cancer cell strains. 62 fresh colorectal adenocarcinoma samples and paired distal normal mucosa were selected in our hospital. They comprised 37 males and 25 females aging 32 to 67 years old with the mean of 43.6. The cellular RNA was extracted, and immunohistochemistry assay was used to detect the expression of MLH1 protein in colorectal cancer, and MSP method was utilized to examine the methylation status of the first exon of MLH1 gene in the tissues. In the 10 cell strains, only the MLH1 mRNAs of SW480 and Caco2 were expressed, and no MLH1 mRNA expression was detected in the other eight strains. The expression level of MLH1 mRNA in the 62 cases of cancer tissue was higher than that in the paired normal mucosa, and MLH1 protein was mainly expressed in the cytoplasm. The expression level of MLH1 protein in adenocarcinoma tissues was significantly higher than that in the paired normal tissue (P<0.01), while the methylation level of cancer tissues was statistically significantly lower than that of the paired normal mucosa (P<0.05). Aberrant DNA methylation dominates the regulation of the MLH1 gene expression changes in colorectal cancer. The results herein provide a theoretical basis for clarifying the differential expressions of MLH1 in colorectal cancer in vitro and in vivo.
A Study on the Aberrant Methylation of Colorectal Cancer MLH1 Gene, American Journal of Clinical and Experimental Medicine.
Vol. 7, No. 1,
2019, pp. 1-6.
Heitman SJ. Hilsden RJ. et al. Correction: Colorectal Cancer Screening for Average-Risk North Americans: An Economic Evaluation [J]. PLoS Med, 2017, 9 (11): 648-52.
Dai Z. Zheng RS. et al. Analysis and prediction of colorectal cancer incidence trend in China [J]. Zhonghua Yu Fang Yi Xue Za Zhi, 2017, 46 (7): 598-603.
Wan DS. Epidemiological trend and control strategy of colorectal cancer in China [J]. Zhonghua Zhong Liu Za Zhi, 2018, 33 (7): 481-3.
Gonzalez-Gonzalez M. Garcia JG. et al. Genomics and proteomics approaches for biomarker discovery in sporadic colorectal cancer with metastasis [J]. Cancer Genomics Proteomics, 2017, 10 (1): 19-25.
Martinez-Uruena N. Alvarez LM. et al. Incidence of -93 MLH1 promoter polymorphism in familialand sporadic colorectal cancer [J]. Colorectal Dis, 2016, 31 (2): 226-9.
Wang T. Liu Y. et al. Association between MLH1 -93G>a polymorphism and risk of colorectal cancer [J]. PLoS One, 2017, 7 (11): 449-51.
Rouleau E. Lefol C. et al. Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome [J]. Hum Mutat, 2017, 30 (6): 867-75.
Zhang Z. Sun D. et al. Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma [J]. PLoS One, 2017, 7 (11): 908-10.
Tsujii M. Cyclooxygenase, cancer stem cells and DNA methylation play important roles in colorectal carcinogenesis [J]. Digestion, 2017, 87 (1):12-6.
Lange CP. Campan M. et al. Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer [J]. PLoS One, 2016, 7 (11): 266-8.
Gao Y. Killian K. et al. Leukocyte DNA methylation and colorectal cancer among male smokers [J]. World J Gastrointest Oncol, 2016, 4 (8): 193-201.
Fang WJ. Zheng Y. et al. Genome-wide analysis of aberrant DNA methylation for identification of potential biomarkers in colorectal cancer patients [J]. Asian Pac J Cancer Prev, 2017, 13 (5): 1917-21.
Williams EA. Folate, colorectal cancer and the involvement of DNA methylation [J]. Proc Nutr Soc, 2017, 71 (4): 592-7.
Bosch LJ. Mongera S. et al. Analytical sensitivity and stability of DNA methylation testing in stool samples for colorectal cancer detection [J]. Cell Oncol (Dordr), 2018, 35 (4): 309-15.
Li BQ. Yu H. et al. MicroRNA Mediated Network and DNA Methylation in Colorectal Cancer [J]. Protein Pept Lett, 2017, 62 (8):556-8.
Xicola RM. Llor X. et al. DNA methylation defects in sporadic and hereditary colorectal cancer [J]. Gastroenterol Hepatol, 2017, 35 (7): 480-7.
Shen Y. Takahashi M. et al. Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells [J]. Cancer Biol Ther, 2018, 13 (7): 542-52.
Zhao ZW. Lian WJ. et al. Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression [J]. Oncol Rep, 2016, 27 (5): 1653-9.
Cassinotti E. Melson J. et al. DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps [J]. Int J Cancer, 2017, 131 (5): 1153-7.
Hinoue T. Weisenberger DJ. et al. Genome-scale analysis of aberrant DNA methylation in colorectal cancer [J]. Genome Res, 2018, 22 (2): 271-82.
Kaneda A. Yagi K. et al. Two groups of DNA methylation markers to classify colorectal cancer into three epigenotypes [J]. Cancer Sci, 2017, 102 (1): 18-24.
Kim JW. Park HM. et al. Polymorphisms in genes involved in folate metabolism and plasma DNA methylation in colorectal cancer patients [J]. Oncol Rep, 2018, 25 (1): 167-72.
Ward RL. Dobbins T. et al. Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry [J]. Genet Med, 2016, 15 (1): 25-35.
Nakanishi R. Kitao H. et al. FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer [J]. Ann Surg Oncol, 2017, 19 (11): 3627-35.