Document Type : Original Article(s)

Authors

1 Department of Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Immunology Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Surgery, Imam Reza Hospital, University Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Background: Aberrant expression level of Hox transcript antisense intergenic RNA (HOTAIR) has been associated with the etiopathogenesis of numerous cancers. Studies on epidemiological data have demonstrated that the risk of susceptibility to colon cancer varies among different populations due to several reasons. In this study, we aimed to assess the expression level of HOTAIR in tumoral tissues of patients with colon cancer and compare it with normal marginal tissues.
Methods: In this case-control study, we recruited a total of 50 patients with colon cancer and collected tumoral and matched marginal tumor free tissues during surgery. Afterwards, we isolated the total RNA from each sample, synthesized cDNA, and performed quantitative analysis by Real-time PCR using the SYBR Green PCR Master Mix in order to measure the transcript level of HOTAIR in samples.
Results: The expression level of HOTAIR was upregulated in tumor tissues compared with normal tumor-free marginal tissues belonging to colon cancer patients (P= 0.0023). Moreover, the expression level of HOTAIR and the clinicopathological specifications of the patients had statistically significant correlations.
Conclusions: HOTAIR may play a role in the development of colon cancer and have the potential for application as a biomarker for colon cancer prognosis.

Keywords

How to cite this article:

Pashapour SH, Shanehbandi D, Bornehdeli S, Zafari V, Mohammad Reza Khani H, Hashemzadeh SH, et al. Overexpression of HOTAIR in tumor tissues of patients with colon cancer correlates with tumor metastasis and differentiation. Middle East J Cancer. 2020;11(4): 410-4. doi: 10.30476 /mejc.2020.81442.101.

1.         Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107(4):1183-8.
2.         Lanza G, Ferracin M, Gafà R, Veronese A, Spizzo R, Pichiorri F, et al.  RNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer. 2007 23;6:54.
3.         Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004;36(4):417-22.
4.         Asadi M, Shanehbandi D, Asvadi Kermani T, Sanaat Z, Zafari V, Hashemzadeh S. Expression level of caspase genes in colorectal cancer. Asian Pac J Cancer Prev. 2018;19(5):1277-80.
5.         Asadi M, Shanehbandi D, Zarintan A, Pedram N, Baradaran B, Zafari V, et al. TP53 gene Pro72Arg (rs1042522) single nucleotide polymorphism as not a risk factor for colorectal cancer in the Iranian Azari population. Asian Pac J Cancer Prev. 2017;18(12):3423-7.
6.         Lamprecht SA, Lipkin M. Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer. 2003;3(8):601-14.
7.         Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629-41. doi: 10.1016/j.cell.2009.02.006.
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. doi: 10.1371/journal.pone.0047998.
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. doi:10.1371/journal.pone.0077070.
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. doi: 10.1245/s10434-011-1581-y.
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. 2011;S5(4). pii: 004.
12.       Xue Y, Gu D, Ma G, Zhu L, Hua Q, Chu H, et al. Genetic variants in lncRNA HOTAIR are associated with risk of colorectal cancer. Mutagenesis. 2015;30(2):303-10. doi: 10.1093/mutage/geu076.
13.       Wu ZH, Wang XL, Tang HM, Jiang T, Chen J, Lu S, et al. Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer. Oncol Rep. 2014;32(1):395-402. doi: 10.3892/or.2014.3186.
14.       Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8.
15.       Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8.
16.     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. doi: 10.1038/nature08975.
17.      Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320-6. doi: 10.1158/0008-5472.
18.       Ishibashi M, Kogo R, Shibata K, Sawada G, Takahashi Y, Kurashige J, et al. Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. Oncol Rep. 2013;29(3):946-50. doi: 10.3892/or.2012.2219.
19.       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. doi: 10.1038/onc.2012.193.
20.       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. doi: 10.1038/nature08975.