Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population

There is an increasing body of evidence which highlights the critical functions of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers. It has been reported that HOX transcript antisense intergenic RNA, a member of long non-coding RNA family, increases breast cancer risk. To date, no data regarding the association between HOX transcript antisense intergenic RNA polymorphisms and the risk of breast cancer development has been reported in Iran. Here, we examine the possible association between HOX transcript antisense intergenic RNA gene polymorphisms and breast cancer in a sample of southeast Iranian female population. The HOX transcript antisense intergenic RNA rs920778, rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases and 231 controls by polymerase chain reaction–restriction fragment length polymorphism. Our findings indicated that rs920778 polymorphism has significant positive association with breast cancer; rs12826786 and rs1899663 polymorphisms demonstrated significant negative association with breast cancer; and the rs4759314 variant was not associated with breast cancer risk. Haplotype analysis revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T haplotype. In conclusion, we investigated only four variants of HOX transcript antisense intergenic RNA gene, and the findings suggest that HOX transcript antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be associated with breast cancer risk in a sample of southeast Iranian population. Further replication studies with other polymorphisms of HOX transcript antisense intergenic RNA gene involving a greater sample size and different ethnicities are necessary to verify our findings.

[1]  A. Sayad,et al.  HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population. , 2017, Gene.

[2]  C. Liang,et al.  Analyzing 37,900 Samples Shows Significant Association between Hotair Polymorphisms and Cancer Susceptibility: A Meta-Analysis , 2017, The International journal of biological markers.

[3]  S. Bayram,et al.  The analysis of lncRNA HOTAIR rs12826786 C>T polymorphism and gastric cancer susceptibility in a Turkish population: lack of any association in a hospital-based case–control study , 2017, Irish Journal of Medical Science (1971 -).

[4]  Xixun Wang,et al.  HOTAIR is a promising novel biomarker in patients with thyroid cancer , 2017, Experimental and therapeutic medicine.

[5]  Huirong Shi,et al.  HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and poor prognosis in a Chinese population. , 2017, Future oncology.

[6]  Wei Zhang,et al.  The HOTAIR, PRNCR1 and POLR2E polymorphisms are associated with cancer risk: a meta-analysis , 2017, Oncotarget.

[7]  S. Ghavami,et al.  Evaluation of the pri-miR-34b/c rs4938723 polymorphism and its association with breast cancer risk. , 2016, Biomedical reports.

[8]  S. Bayram,et al.  A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case–control study , 2016, Tumor Biology.

[9]  Jian-zhong Li,et al.  Salivary HOTAIR and PVT1 as novel biomarkers for early pancreatic cancer , 2016, Oncotarget.

[10]  J. Dou,et al.  Decreasing lncRNA HOTAIR expression inhibits human colorectal cancer stem cells. , 2016, American journal of translational research.

[11]  M. Taheri,et al.  Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population , 2016, Breast cancer : basic and clinical research.

[12]  Qiang Yu,et al.  Elevated expression of long intergenic non‐coding RNA HOTAIR in a basal‐like variant of MCF‐7 breast cancer cells , 2015, Molecular carcinogenesis.

[13]  L. Dai,et al.  Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population. , 2015, Cancer epidemiology.

[14]  M. Hashemi,et al.  Effect of TP53 16-bp and β-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer. , 2015, Gene.

[15]  Qiang Chen,et al.  Estradiol induces HOTAIR levels via GPER-mediated miR-148a inhibition in breast cancer , 2015, Journal of Translational Medicine.

[16]  M. Hajjari,et al.  HOTAIR: an oncogenic long non-coding RNA in different cancers , 2015, Cancer biology & medicine.

[17]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[18]  S. Bayram,et al.  Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population , 2015, Tumor Biology.

[19]  Young Tae Kim,et al.  Long non-coding RNA HOTAIR is associated with human cervical cancer progression , 2014, International journal of oncology.

[20]  Yin Zheng,et al.  Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells , 2014, Tumor Biology.

[21]  M. Zheng,et al.  Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer , 2014, Archives of Gynecology and Obstetrics.

[22]  M. Taheri,et al.  hsa-mir-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population. , 2014, Biomarkers in medicine.

[23]  J. Rinn,et al.  Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination , 2013, Nature Communications.

[24]  M. Larsen,et al.  Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer , 2013, Breast Cancer Research and Treatment.

[25]  G. Wakabayashi,et al.  Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. , 2013, Oncology reports.

[26]  Rong Yin,et al.  Long noncoding RNA: an emerging paradigm of cancer research , 2013, Tumor Biology.

[27]  Gianluca Gregori,et al.  Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer , 2012, Breast Cancer Research and Treatment.

[28]  S. Safe,et al.  HOTAIR IS A NEGATIVE PROGNOSTIC FACTOR AND EXHIBITS PRO-ONCOGENIC ACTIVITY IN PANCREATIC CANCER , 2012, Oncogene.

[29]  M. Esteller Non-coding RNAs in human disease , 2011, Nature Reviews Genetics.

[30]  S. Miyano,et al.  Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. , 2011, Cancer research.

[31]  A. Chinnaiyan,et al.  The emergence of lncRNAs in cancer biology. , 2011, Cancer discovery.

[32]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[33]  Carolyn J. Brown,et al.  The functional role of long non-coding RNA in human carcinomas , 2011, Molecular Cancer.

[34]  Haiyang Xie,et al.  Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation , 2011, Annals of Surgical Oncology.

[35]  Leonard Lipovich,et al.  MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. , 2010, Biochimica et biophysica acta.

[36]  C. Harris,et al.  Genetic variation in microRNA networks: the implications for cancer research , 2010, Nature Reviews Cancer.

[37]  D. Evans,et al.  Assessing women at high risk of breast cancer: a review of risk assessment models. , 2010, Journal of the National Cancer Institute.

[38]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[39]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[40]  D. Spector,et al.  Long noncoding RNAs: functional surprises from the RNA world. , 2009, Genes & development.

[41]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[42]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[43]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[44]  Joan Valls,et al.  SNPStats: a web tool for the analysis of association studies , 2006, Bioinform..

[45]  T. Hudson,et al.  Influence of human genome polymorphism on gene expression. , 2006, Human molecular genetics.

[46]  A. Levine,et al.  A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. , 2005, Cancer research.

[47]  Yuan Yuan,et al.  A systematic review and meta-analysis of the association between long non-coding RNA polymorphisms and cancer risk. , 2017, Mutation research.

[48]  Chuan-Jen Hsu,et al.  Identification of a novel GATA3 mutation in a deaf Taiwanese family by massively parallel sequencing. , 2015, Mutation research.

[49]  H. Fujii,et al.  A case of male noninvasive intracystic papillary carcinoma forming a tumor in the nipple duct , 2003, Breast cancer.

[50]  Maciej Szymanski,et al.  Non-coding, mRNA-like RNAs database Y2K , 2000, Nucleic Acids Res..