Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the long non-coding RNAs that plays an important role in invasion, cell proliferation and metastasis of various cancers. However, insufficient information on the association of MALAT1 with the methylation process and its role in the development of colorectal cancer is not yet fully available. This study set out to determine the effect of methylation on MALAT1 gene in primary colorectal lesions and tumors to gain further knowledge about the diagnostic and prognostic value of MALAT1.
Materials and methods
Methylation Pattern of MALAT1 promoter determined by Methylation-Specific Polymerase Chain Reaction (MSP) in 86 colorectal primary lesions, tumors and normal specimens. MALAT1 methylation pattern was compared in tumor and polyp tissue. In order to obtain more accurate results, we investigated the association of MALAT1 promoter methylation pattern with clinicopathologic factors in patients.
The results indicated that the MALAT1 promoter methylation pattern in tumor tissue, primary lesions tissue and normal was not significant difference (p=0.430). Moreover, compared, the MALAT1 promoter methylation pattern between polyp types and tumor tissue groups was not significant (p=0.437). Surprisingly, the methylation frequency of MALAT1 methylation was significantly higher in colon lesions in comparison with their rectum lesion, p = 0.035. In addition, significant hypermethylation of MALAT1 was not observed between the other patients’ clinicopathological data at both polyps 46/66 and tumor tissue 20/66.
This study suggests that the MALAT1 promoter methylation pattern in patients with colorectal primary lesions and tumors compared with normal tissue as not a significant risk factor for colorectal cancer. Moreover, clearance the significantly higher methylation frequency in colon lesions in comparison with their rectum lesion need to be further explored.
Fund, W.C.R. and A.I.f.C. Research, Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Vol. 1. 2007: Amer Inst for Cancer Research.
Boyle, P. and M.J.J.B. Langman, ABC of colorectal cancer: Epidemiology. 2000. 321(Suppl S6): p. 0012452.
Haggar, F.A., R.P.J.C.i.c. Boushey, and r. surgery, Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. 2009. 22(04): p. 191-197.
Croome, K.P., G.J. Gores, and C.B. Rosen, Surgical Treatment of Primary Sclerosing Cholangitis, in Shackelford's Surgery of the Alimentary Tract, 2 Volume Set. 2019, Elsevier. p. 1378-1385.
Bekkink, M.O., C. McCowan, G. Falk, et al., Diagnostic accuracy systematic review of rectal bleeding in combination with other symptoms, signs and tests in relation to colorectal cancer. 2010. 102(1): p. 48.
Noffsinger, A.E.J.A.R.o.P.M.D., Serrated polyps and colorectal cancer: new pathway to malignancy. 2009. 4: p. 343-364.
Levine, J.S. and D.J.J.N.E.J.o.M. Ahnen, Adenomatous polyps of the colon. 2006. 355(24): p. 2551-2557.
Aghdaei, H.A., E.N. Mojarad, S. Ashtari, et al., Polyp detection rate and pathological features in patients undergoing a comprehensive colonoscopy screening. 2017. 8(1): p. 3.
Aarons, C.B., S. Shanmugan, and J.I.J.W.J.o.G.W. Bleier, Management of malignant colon polyps: current status and controversies. 2014. 20(43): p. 16178.
Schachschal, G., S. Sehner, M. Choschzick, et al., Impact of reassessment of colonic hyperplastic polyps by expert GI pathologists. 2016. 31(3): p. 675-683.
Cannizzaro, R., R. Magris, S. Maiero, M. Fornasarig, and V. Canzonieri, Classification of Colon Polyps and Risk of Neoplastic Progression, in Colon Polypectomy. 2018, Springer. p. 1-11.
Ranjbar, R., V. Chaleshi, H.A. Aghdaei, and S.J.M. Morovvati, Investigating the association between miR-608 rs4919510 and miR-149 rs2292832 with Colorectal Cancer in Iranian Population. 2018. 7(2): p. 100-106.
Chaleshi, V., R. Tajali, S. Savabkar, et al., Lack of association between NOD2 rs3135500 and IL12B rs1368439 microRNA binding site SNPs and colorectal cancer susceptibility in an Iranian population. 2016. 5(2): p. 152-156.
Peng, C., S. Han, H. Zhang, and Y.J.I.j.o.m.s. Li, RPITER: A Hierarchical Deep Learning Framework for ncRNA–Protein Interaction Prediction. 2019. 20(5): p. 1070.
Wilusz, J.E., H. Sunwoo, D.L.J.G. Spector, and development, Long noncoding RNAs: functional surprises from the RNA world. 2009. 23(13): p. 1494-1504.
Mercer, T.R., M.E. Dinger, and J.S.J.N.r.g. Mattick, Long non-coding RNAs: insights into functions. 2009. 10(3): p. 155.
Guo, F., L. Guo, Y. Li, et al., MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation. 2015. 8(12): p. 15903.
Gutschner, T., M. Hämmerle, M. Eißmann, et al., The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. 2013. 73(3): p. 1180-1189.
Arun, G. and D.L.J.R.b. Spector, MALAT1 long non-coding RNA and breast cancer. 2019. 16(6): p. 860-863.
Lin, R., S. Maeda, C.a. Liu, M. Karin, and T.J.O. Edgington, A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. 2007. 26(6): p. 851.
Wang, X., M. Li, Z. Wang, et al., Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. 2015. 290(7): p. 3925-3935.
Yang, L., C. Lin, W. Liu, et al., ncRNA-and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. 2011. 147(4): p. 773-788.
Guil, S., M. Soler, A. Portela, et al., Intronic RNAs mediate EZH2 regulation of epigenetic targets. 2012. 19(7): p. 664.
Gospodarowicz, M.K., J.D. Brierley, and C. Wittekind, TNM classification of malignant tumours. 2017: John Wiley & Sons.
Pandey, G.K., S. Mitra, S. Subhash, et al., The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. 2014. 26(5): p. 722-737.
Li, X., N. Chen, L. Zhou, et al., Genome-wide target interactome profiling reveals a novel EEF1A1 epigenetic pathway for oncogenic lncRNA MALAT1 in breast cancer. 2019. 9(4): p. 714.
Guo, F., Y. Li, Y. Liu, et al., Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. 2010. 42(3): p. 224-229.
Wang, W., Y. Zhu, S. Li, et al., Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-catenin via Ezh2. 2016. 7(18): p. 25668.
Vassallo, I., P. Zinn, M. Lai, et al., WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1. 2016. 35(1): p. 12.
Tee, A.E., D. Ling, C. Nelson, et al., The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. 2014. 5(7): p. 1793.
Okugawa, Y., Y. Toiyama, K. Hur, et al., Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. 2014. 35(12): p. 2731-2739.
Fu, X., Y. Liu, C. Zhuang, et al., Synthetic artificial microRNAs targeting UCA1-MALAT1 or c-Myc inhibit malignant phenotypes of bladder cancer cells T24 and 5637. 2015. 11(5): p. 1285-1289.
Xu, C., M. Yang, J. Tian, X. Wang, and Z.J.I.j.o.o. Li, MALAT-1: a long non-coding RNA and its important 3'end functional motif in colorectal cancer metastasis. 2011. 39(1): p. 169-175.
Hu, L., Y. Wu, D. Tan, et al., Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. 2015. 34(1): p. 7.
Hutchinson, J.N., A.W. Ensminger, C.M. Clemson, et al., A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. 2007. 8(1): p. 39.
Tripathi, V., J.D. Ellis, Z. Shen, et al., The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. 2010. 39(6): p. 925-938.
Amort, T., D. Rieder, A. Wille, et al., Distinct 5-methylcytosine profiles in poly (A) RNA from mouse embryonic stem cells and brain. 2017. 18(1): p. 1.
Wang, X., L. Sehgal, N. Jain, et al., LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2. 2016. 14(1): p. 346.
Sun, Y. and L.J.C. Ma, New insights into long non-coding RNA malat1 in cancer and metastasis. 2019. 11(2): p. 216.
Liang, J., L. Liang, K. Ouyang, et al., MALAT 1 induces tongue cancer cells' EMT and inhibits apoptosis through Wnt/β‐catenin signaling pathway. 2017. 46(2): p. 98-105.