Upregulation of HOTAIR Transcript Level in Tumor Tissue of Iranian Women with Breast Cancer

Document Type: Original Article


1 Master of Science, Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

2 Professor, Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

3 Assistant Professor, Department of Biology, Faculty of Science, Azarbaijan Shahid Madani University, Tabriz, Iran

4 Associate Professor, Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

5 Department of Biology, Faculty of Science, Azerbaijan Shahid Madani University, Tabriz, Iran


Background:Dysregulation of HOX Transcript Antisense Intergenic RNA (HOTAIR) has been linked to the etiopathogenesis of several human cancers. According to epidemiological evidences, the risk of susceptibility to breast cancer varies among different populations. This study was designed to determine the transcriptional level of HOTAIR in tumor cells of breast cancer patients compared to normal marginal cells and to identify if this molecule has the potential to be considered as a biomarker in the prognosis of breast cancer.
Methods:A total of 37 patients with breast cancer were recruited. Tumor and matched normal tumor-free margin samples were collected during surgery from each patient. Following total RNA extraction and cDNA synthesis, quantitative analysis was performed by real-time PCR using the SYBR Green PCR Master Mix to determine the transcript level of HOTAIR in samples.
Results:It was observed that mRNA expression level of HOTAIR was upregulated in tumor cells compared with normal tumor free marginal cells of breast cancer patients (Fold change= +6.9; P = 0.0001). However, no statistically significant correlations were observed between the mRNA expression level of HOTAIR and clinicopathological manifestations of the patients.
Conclusions:The results were in accord with what had previously been reported and therefore, it can be concluded that in Iranian population, too, HOTAIR is upregulated in tumor cells of breast cancer patients and has the potential to be considered as a biomarker for the prognosis of breast cancer.


  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12):2893-917.
  2. Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol 2009; 20(3):556-63.
  3. Namba R, Maglione JE, Young LJ, Borowsky AD, Cardiff RD, MacLeod CL, et al. Molecular characterization of the transition to malignancy in a genetically engineered mouse-based model of ductal carcinoma in situ11National Cancer Institute grants CA89140-01 (RD Cardiff and JP Gregg) and 5R01CA81736 (CL MacLeod), Department of Defense grant DAMD 17-03-1-0666 (CL MacLeod), California Breast Cancer Research Program grants 6KB-0074 (JP Gregg) and 9FB-0212 (R. Namba), National Centers for Research Resources grant U42RR14905, and IF Smith Foundation. Molecular Cancer Research 2004; 2(8):453-63.
  4. Charpentier A, Aldaz CM. The Molecular Basis of Breast Carcinogenesis. Totowa, NJ: Humana Press; 2002. p 347-63.
  5. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. cell 2007; 129(7):1311-23.
  6. Woo CJ, Kingston RE. HOTAIR lifts noncoding RNAs to new levels. Cell 2007; 129(7):1257-9.
  7. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010; 464(7291):1071-6.
  8. Chisholm KM, Wan Y, Li R, Montgomery KD, Chang HY, West RB. Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PloS one 2012; 7(10):e47998.
  9. Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, et al. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PloS one 2013; 8(10):e77070.
  10. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol 2011; 18(5):1243-50.
  11. Milhem MM, Knutson T, Yang S, Zhu D, Wang X, Leslie KK, et al. Correlation of MTDH/AEG-1 and HOTAIR expression with metastasis and response to treatment in sarcoma patients. J Cancer Sci Ther 2012; Suppl 5(4):004.
  12. Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, et al. Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat 2012; 136(3):875-83.
  13. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 2001; 29(9):e45.
  14. Yu X, Li Z. Long non-coding RNA HOTAIR: a novel oncogene (Review). Mol Med Rep 2015; 12(4):5611-8.
  15. Orlando V. Polycomb, epigenomes, and control of cell identity. Cell 2003; 112(5):599-606.
  16. Mohammad HP, Cai Y, McGarvey KM, Easwaran H, Van Neste L, Ohm JE, et al. Polycomb CBX7 promotes initiation of heritable repression of genes frequently silenced with cancer-specific DNA hypermethylation. Cancer Res 2009; 69(15):6322-30.
  17. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 2006; 6(11):846-56.
  18. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003; 100(20):11606-11.
  19. Li D, Feng J, Wu T, Wang Y, Sun Y, Ren J, et al. Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am J Pathol 2013; 182(1):64-70.
  20. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 2013; 32(13):1616-25.