Long non-coding RNA (lncRNA) MALAT1 was firstly identified in 2003 as transcript associated with metastasis in patients with early-stage of non-small cell lung cancer. Today, it is believed that MALAT1’s primary function is the regulation of expression of genes which products are involved in metastases formation. However, there are currently few publications dealing with association of MALAT1 gene single-nucleotide polymorphisms with the onset of oncological pathologies of different localization, and to investigating its association with various characteristics and stages of tumor process, including metastasis. The purpose of the study was to find possible relation between MALAT1 gene rs3200401 polymorphism and metastasis development in Ukrainian patients with bladder cancer. Materials and methods. Whole venous blood of 141 patients with transitional cell carcinoma of urinary bladder was used for study. Genotyping of MALAT1 gene rs3200401 polymorphic site was performed by Real-time PCR using 7500 Fast Real-time PCR System (Applied Biosystems, Foster City, USA) and Taq-Man Assays (TaqMan®SNP Assay C_3246069_10). Statistical analysis was done using SPSS software package (version 17.0). Binary and multivariable logistic regression techniques were used to find the possible genotype association between MALAT1 gene rs3200401 site and metastasis development. P values > 0.05 were considered to be statistically significant. Results and discussion. The comparative analysis of MALAT1 gene rs3200401 genotypes distribution between patients with and without metastases revealed no significant difference (P = 0.074), while T and C alleles frequencies significantly different between comparison groups (P = 0.015). In addition, it was found out that the risk of metastases development in minor T-allele carriers with transitional cell carcinoma of urinary bladder was 2.2 times higher compared with the individuals with CC-genotype (Pobs=0.048; ORobs=2.207; 95% CI=1.006-4.844). However, after adjustment for age, gender, smoking habits and alcohol abuse the significant association was lost (Padj=0.279; ORadj=0.678; 95% CI=0.335-1.371). Conclusion. The study results showed that there was a relation between MALAT1 gene rs3200401 polymorphism and metastasis development in Ukrainian patients with transitional cell carcinoma of urinary bladder. Minor T allele carriers have higher risk of bladder cancer metastasis onset compared to major C allele homozygotes.

Keywords: long noncoding RNA, MALAT1, bladder cancer

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1. Gibb A, Brown C, Lam W. The functional role of long non-coding RNA in human carcinomas. Carolyn Mol Cancer. 2011; 10: 38. PMID: 21489289. PMCID: PMC3098824. https://doi.org/10.1186/1476-4598-10-38
2. Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, et la. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 2015; 75: 1322-31. PMID: 25600645. PMCID: PMC5884967. https://doi.org/10.1158/0008-5472.CAN-14-2931
3. Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics. 2007. PMID: 17270048. PMCID: PMC1800850. https://doi.org/10.1186/1471-2164-8-39
4. Ji P, Diederichs S, Wang W, Böing S, Metzger R. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003; 22(39): 8031-41. PMID: 12970751. https://doi.org/10.1038/sj.onc.1206928
5. Ma X, Wang J, Wang L, Ma C, Wang X, Liu F. MALAT1 as an evolutionarily conserved lncRNA, plays a positive role in regulating proliferation and maintaining undifferentiated status of early-stage hematopoietic cells. BMC Genomics. 2015; 16(1): 676. PMID: 26335021. PMCID: PMC4559210. https://doi.org/10.1186/s12864-015-1881-x
6. Li M, Wang Y, Cheng L, Niu W, Zhao G. Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications. Oncotarget. 2017; 8(29): 48424-35. https://doi.org/10.18632/oncotarget.17053
7. Sun Y, Ma L. New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis. Cancers. 2019; 11(2): E216. PMID: 30781877. PMCID: PMC6406606. https://doi.org/10.3390/cancers11020216
8. Zhang HM, Yang FQ, Chen SJ, Che J, Zheng JH. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. 2015; 36(4): 2947-55. PMID: 25480417. https://doi.org/10.1007/s13277-014-2925-6
9. Zhang X, Hamblin H, Yin KJ. The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 2017; 14(12): 1705-14. PMID: 28837398. PMCID: PMC5731810. https://doi.org/10.1080/15476286.2017.1358347
10. Wu Y, Huang C, Meng X, Li J. Long Noncoding RNA MALAT1: Insights into its Biogenesis and Implications in Human Disease. Curr Pharm Des. 2015; 21(34): 5017-28. PMID: 26205289. https://doi.org/10.2174/1381612821666150724115625
11. Wang JZ, Xiang JJ, Wu GL, Bai YS, Chen ZW. A genetic variant in long non-coding RNA MALAT1 associated with survival outcome among patients with advanced lung adenocarcinoma: a survival cohort analysis. BMC Cancer. 2017; 17(1): 167. PMID: 28253859. PMCID: PMC5335789. https://doi.org/10.1186/s12885-017-3151-6
12. Peng R, Luo C, Guo Q, Cao J, Yang Q, Dong K. Association analyses of genetic variants in long non-coding RNA MALAT1 with breast cancer susceptibility and mRNA expression of MALAT1 in Chinese Han population. Gene. 2018; 642: 241-8. PMID: 29146194. https://doi.org/10.1016/j.gene.2017.11.013