Analysis of ANRIL gene polymorphism rs4977574 association with kidney cancer development in Ukrainian population.
DOI:
https://doi.org/10.26641/2307-0404.2020.2.206360Keywords:
long non-coding RNA, ANRIL, gene polymorphism, kidney cancerAbstract
ANRIL (Antisense Non-coding RNA in the INK4 Locus, also known as CDKN2B-AS1) – 3.8-kb long non-coding RNA transcribed from the antisense strand of INK4b-ARF-INK4a gene cluster. It is known that ANRIL overexpression is associated with development of oncological pathologies of different localization. In addition, there are a number of studies devoted to role of ANRIL genetic polymorphism in emergence and progression of tumors, including tumors of genitourinary system. The aim of the study was to check the possible association between ANRIL gene polymorphism rs4977574 and kidney cancer development in representatives of Ukrainian population. Whole venous blood of 101 patients with clear cell renal cell carcinoma (CCRCC) (42 women and 59 men) and 100 patients without oncology history (34 women and 66 men) was used in the study. DNA from blood white cells was extracted using GeneJET Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific, USA). Genotyping of rs4977574 ANRIL gene polymorphic locus was performed using real-time polymerase chain reaction (real-time PCR) method in the presence of TaqMan assay C_31720978_30. The mathematical data were processed using the SPSS software package (version 17.0). P values <0.05 were considered as statistically significant. It was found that difference in rs4977574-genotype distribution between patients with CCRCC and control persons was absent in general group (P=0.216). At the same time, the statistical analysis stratified by gender showed that both in female and male subjects rs4977574-genotypes frequency also did not differ significantly between comparison groups (P=0.526 and P=0.160, respectively). However, after adjusting for age, body mass index, and smoking habits statistically significant association between rs4977574 ANRIL gene polymorphism and risk of kidney cancer development was detected in male subjects under superdominant inheritance model (P=0.049). It was revealed that heterozygotes (AG-genotype) have 2.17-fold higher risk of CCRCC development (95% CI=1.005-4.695) compared to patients with AA- and GG-genotypes. In summary, this is the first report about ANRIL gene polymorphisms association with kidney cancer. Obtained results revealed that rs4977574 is related to kidney cancer risk only in Ukrainian men. Male individuals with AG-genotype have higher risk of CCRCC development compared to AA- and GG-genotypes carriers.References
[About the Approving of Conducting of Medicines Clinical Trials Procedure and Expertise of Clinical Trials Materials, and the Model Regulations on Ethics Committees: Order of the Ministry of Health of Ukraine No. 690]. 2009. September 23. Ukrainian.
Khorshidi H, Taheri M, Noroozi R, Sarrafzadeh S, Sayad A, Ghafouri-Fard S. ANRIL Genetic Variants in Iranian Breast Cancer Patients. Cell J. 2017;19(Suppl 1):72-78. doi: https://doi.org/10.22074/cellj.2017.4496
Taheri M, Pouresmaeili F, Omrani MD, Habibi M, Sarrafzadeh S, Noroozi R, et al. Association of ANRIL gene polymorphisms with prostate cancer and benign prostatic hyperplasia in an Iranian population. Biomark Med. 2017;11(5):413-22. doi:https://doi.org/10.2217/bmm-2016-0378
Gong WJ, Yin J, Li XP, Fang C, Xiao D, Zhang W, et al. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol. 2016;37(6):8349-58. doi: https://doi.org/10.1007/s13277-015-4497-5
Czarnecka A, Niedzwiedzka M, Porta C, Szczylik C. Hormone signaling pathways as treatment targets in renal cell cancer (Review). Int J Oncol. 2016;48(6):2221-35. doi: https://doi.org/10.3892/ijo.2016.3460
Dianatpour A, Ghafouri-Fard S. The Role of Long Non Coding RNAs in the Repair of DNA Double Strand Breaks. Int J Mol Cell Med. 2017;6(1):1-12.
Meseure D, Vacher S, Alsibai KD, Nicolas A, Chemlali W, et al. Expression of ANRIL-Polycomb Complexes-CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value. Mol Cancer Res. 2016;(7):623-33.
Gamell C, Ginsberg D, Haupt S, Haupt Y. New insights on the regulation of INK4/ARF locus expression. Oncotarget. 2017;8(63):106147-8. doi: https://doi.org/10.18632/oncotarget.22258
Liu P, Zhang M, Niu Q, Zhang F, Yang Y, Jiang X. Knockdown of long non-coding RNA ANRIL inhibits tumorigenesis in human gastric cancer cells via microRNA-99a-mediated down-regulation of BMI1. Braz J Med Biol Res. 2018;51(10):e6839. doi: https://doi.org/10.1590/1414-431x20186839
Kong Y, Hsieh C, Alonso L. ANRIL: A lncRNA at the CDKN2A/B Locus With Roles in Cancer and Metabolic Disease. Front Endocrinol (Lausanne). 2018;9:405. doi: https://doi.org/10.3389/fendo.2018.00405
Zhu H, Li X, Song Y, Zhang P, Xiao Y, Xing Y. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway. Biochem Biophys Res Commun. 2015;467(2):223-28. doi: https://doi.org/10.1016/j.bbrc.2015.10.002
Fanelli G, Gasparini P, Coati I, Cui R, Pakula H, Chowdhury B. Long-noncoding RNAs in gastroesophageal cancers. Noncoding RNA Res. 2018;3(4):195-212. doi: https://doi.org/10.1016/j.ncrna.2018.10.001
Zhai W, Ma J, Zhu R, Xu C, Zhang J, Chen Y, et al. MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis. Br J Cancer. 2018;119(5):591-604. doi: https://doi.org/10.1038/s41416-018-0196-5
Tritto V, Ferrari L, Esposito S, Zuccotti P, Bianchessi D, Natacci F. Non-Coding RNA and Tumor Development in Neurofibromatosis Type 1: ANRIL rs2151280 Is Associated with Optic Glioma Development and a Mild Phenotype in Neurofibromatosis Type 1 Patients. Genes (Basel). 2019;10(11): E892. doi: https://doi.org/10.3390/genes10110892
Zhao B, Lu Y, Yang Y, Hu L, Bai Y, Li R, et al. Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-β1/ Smad signaling pathway. Cancer Biomark. 2018;21(3):613-620. doi: https://doi.org/10.3233/CBM-170683
Poi M, Li J, Sborov D, VanGundy Z, Cho Y, Lamprecht M, et al. Polymorphism in ANRIL is associated with relapse in patients with multiple myeloma after autologous stem cell transplant. Mol Carcinog. 2017;56(7):1722-32. doi: https://doi.org/10.1002/mc.22626
Powles T, Albiges L, Staehler M, Bensalah K, Dabestani S, Giles R. Updated European Association of Urology Guidelines Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer. Eur Urol. 2017;pii: S0302-2838(17)31001-1. doi: https://doi.org/10.1016/j.eururo.2017.11.016
Ward LD, Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 2016;44(D1):D877-881. doi: https://doi.org/10.1093/nar/gkv1340
Downloads
How to Cite
Issue
Section
License
Copyright (c) 2020 Medicni perspektivi (Medical perspectives)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.
