Volkogon A. D., Chumachenko Ya. D., Harbuzova V. Yu., Ataman О. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

MALAT1 (metastatic associated lung adenocarcinoma transcript 1) is one of the most well-known and most conserved long non-coding RNA (lncRNA). This lncRNA is considered to be the biomarker of prostate cancer (PC) increased risk, and high expression of its gene correlates with the worst survival rate in patients with PC. The link between MALAT1 genetic polymorphisms and different variants of malignant tumors is less studied. Wherein, studies of association between MALAT1 gene SNPs and PC risk are absent at all. The aim of the study was to analyze the possible link between rs3200401 locus of lncRNA MALAT1 gene and prostate adenocarcinoma (PA) development in Ukrainian population. Object and methods. Venous blood of 184 patients with PA (mean age 73.03 ± 7.56 years) and 66 men (mean age 76.8 ± 9.05 years) without cancer was used for case-control study. MALAT1 rs3200401 polymorphism genotyping was performed by real-time PCR method using 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, USA) and Taq-Man Assays (TaqMan®SNP Assay C_3246069_10). The statistical analysis of obtained data was performed using SPSS (version 17.0, Chicago, IL, USA). All statistical tests were two-sided, P <0.05 was considered significant. Results. The comparative analysis of rs3200401 MALAT1 alleles distribution between PA patients and control individuals did not show a significant difference (P = 0.095). Instead, the difference in genotypes distribution between the comparison groups was statistically significant (P = 0.005). Before adjustment for non-genetic risk factors the link between rs3200401 site and AP development was revealed for recessive and additive models. It was found that minor T-alleles homozygotes had significantly lower risk of PC development compared to C-allele carriers (OR = 0.161; P = 0.004) and C-allele homozygotes (OR = 0.168; P = 0.005). After adjusting for age, smoking status and BMI the overall picture of the results did not change: OR = 0.164; a = 0.005 – for recessive model; OR = 0.170; Pa = 0.006 – for additive model). Conclusion. The obtained results showed that MALAT1 rs3200401 locus was associated with the prostate adenocarcinoma onset in Ukrainian men. TT-genotype carriers have the lower risk of prostate adenocarcinoma development compared to C-alleles carriers.

long non-coding RNA, MALAT1, gene polymorphism, prostate cancer. Р

1. Jalali S, Kapoor S, Sivadas A, Bhartiya D, Scaria V. Computational approaches towards understanding human long non-coding RNA biology. Bioinformatics. 2015;31(14):2241-51.
2. Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P, et al. MALAT1: a druggable long non-coding RNA for targeted anticancer approaches. J Hematol Oncol. 2018;11(1):63.
3. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010;220(2):126-39.
4.  Akhade VS, Pal D, Kanduri C. Long Noncoding RNA: Genome Organization and Mechanism of Action. Adv Exp Med Biol. 2017;1008:47-74.
5. Gutschner T, Hämmerle M, Diederichs S. MALAT1 – a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl). 2013;91(7):791- 801.
6.  Lin Y, Schmidt B, Bruchez M, McManus CJ. Structural analyses of NEAT1 lncRNAs suggest long-range RNA interactions that may contribute to paraspeckle architecture. Nucleic Acids Res. 2018;46(7):3742-52.
7. Tripathi V, Ellis J, Shen Z, Song DY, Pan Q, Watt AT, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39(6):925-38.
8. Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, et al. 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.
9.  Wu X, Wang X, Wu W, Hu YP, Li ML, Ding Q, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15(6):806-14.
10. Danyang R, Huiying L, Renqiu Li, Sun J, Guo P, Han H, et al. Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications (Review). Oncol Lett. 2016;11(3):1621-30.
11. Martens-Uzunova E, Böttcher R, Croce C, Jenster G, Visakorpi T, Calin GA. Long noncoding RNA in prostate, bladder, and kidney cancer. Eur Urol. 2014;65(6):1140-51.
12. Smolle M, Bauernhofer T, Pummer K, Calin G, Pichler M. Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer. Int J Mol Sci. 2017;18(2):473.
13. Li C, Cui Y, Liu L, Ren W, Li Q, Zhou X, et al. High Expression of Long Noncoding RNA MALAT1 Indicates a Poor Prognosis and Promotes Clinical Progression and Metastasis in Bladder Cancer. Clin Genitourin Cancer. 2017;15(5):570-6.
14. Miyagawa R, Tano K, Mizuno R, Nakamura Y, Ijiri K, Rakwal R, et al. Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles. RNA. 2012;18(4):738-51.
15. Wang J, Xiang J, Wu L, Bai, Y, Chen Z, Yin Z, et al. 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;17:167.
16. Peng R, Luo C, Guo Q, Cao J, Yang Q, Dong K, et al. 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.

«Bulletin of problems biology and medicine» Issue 2 Part 1 (150), 2019 year, 109-112 pages, index UDK 616.6-006:577.213/.216

10.29254/2077-4214-2019-2-1-150-109-112