THE STUDY OF ASSOCIATION BETWEEN HOTAIR GENE rs1899663 POLYMORPHISM AND METASTASIS DEVELOPMENT IN PROSTATE CANCER PATIENTS

Volkogon A. D.

MEDICAL GENETICS

Scentific article

HOTAIR (HOX antisense intergenic RNA) is involved in regulation of many target genes expression at both epigenetic and transcriptional levels. It is known that HOTAIR leads to tumors development by methylation of Lys-27 residues (H3K27) and demethylation of Lys-4 residues (H3K4) of H3 histones of genes involved in cell division. It has been demonstrated that prostate cancer (PC) progression is associated with significant increase of HOTAIR transcripts number in malignant prostate cells. In addition, it is known that HOTAIR overexpression stimulates the PC cells proliferation, and HOTAIR knockdown leads to division suppression of malignant prostate cells. The aim of the study was to study of the possible association between HOTAIR gene rs1899663 locus and metastasis development in Ukrainian prostate cancer patients. Object and methods. The venous blood of PC 184 patients (80 with metastasis and 104 without metastatic signs) was used in current case-control study. Genotyping of participants by HOTAIR gene rs1899663-site was carried out by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR-RFLP). Statistical analysis of obtained data was performed using SPSS 17.0 software package (Chicago, IL, USA). P values < 0.05 were considered as statistically significant. Results. It was revealed that frequency of GG-, GT-, and TT-genotypes (HOTAIR gene rs1899663 site) did not differ significantly between PC patients without metastases and with metastatic process signs (P = 0.291). Statistically significant association between different rs1899663-allelic variants and metastasis development in PC patients was not found both before and after adjusting for age, body mass index, smoking, and alcohol abuse (P > 0.05). Conclusion. Thus, this study results showed that HOTAIR gene rs1899663 polymorphic locus is not involved in metastasis occurrence in Ukrainian men with prostate cancer.

long non-coding RNA, HOTAIR, nucleotide polymorphism, metastasis, prostate cancer.

1. Bussemakers M, van Bokhoven A, Verhaegh G, Smit F, Karthaus H, Schalken J, et al. DD3: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 1999;59(23):5975-9.
2. Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med. 2015;12(1):1-9.
3. Cai B, Song XQ, Cai JP, Zhang S. HOTAIR: a cancer-related long non-coding RNA. Neoplasma. 2014;61(4):379-91.
4. Zhang A, Zhao J, Kim J, Fong K, Yang Y, Chakravarti D, et al. LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep. 2015;13(1):209-21.
5. Li H, Tang XM, Liu Y, Li W, Chen Q, Pan Y. Association of Functional Genetic Variants of HOTAIR with Hepatocellular Carcinoma (HCC) Susceptibility in a Chinese Population. Cell Physiol Biochem. 2017;44(2):447-54.
6. Weng SL, Wu WJ, Hsiao YH, Yang SF, Hsu CF, Wang PH. Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer. Int J Med Sci. 2018;15(12):1312-9.
7. Guo L, Lu X, Zheng L, Liu X, Hu M. Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population. PLoS One. 2016;e0160039.
8. Su SC, Hsieh MJ, Lin CW, Chuang CY, Liu YF, Yeh CM, Yang SF. Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer. J Dent Res. 2018;97(6):717-24.
9. Taheri M, Habibi M, Noroozi R, Rakhshan A, Sarrafzadeh S, Sayad A, et al. HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population. Gene. 2017;613:20-4.
10. Volkogon A. Investigation the role of long non-coding RNA HOTAIR genetic polymorphism in prostate adenocarcinoma development. Urology. 2019;23(3):217-23.
11. Gong WJ, Yin JY, 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.

«Bulletin of problems biology and medicine» Issue 4 Part 2 (154), 2019 year, 259-262 pages, index UDK 616.6-006:577.213/.216

10.29254/2077-4214-2019-4-2-154-259-262