Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer

Wu,Ze-Hua; Wang,Xiao-Liang; Tang,Hua-Mei; Jiang,Tao; Chen,Jian; Lu,Su; Qiu,Guo-Qiang; Peng,Zhi-Hai; Yan,Dong-Wang

doi:10.3892/or.2014.3186

Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer

Authors:
- Ze-Hua Wu
- Xiao-Liang Wang
- Hua-Mei Tang
- Tao Jiang
- Jian Chen
- Su Lu
- Guo-Qiang Qiu
- Zhi-Hai Peng
- Dong-Wang Yan
View Affiliations

Affiliations: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China, Department of Pathology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China
Published online on: May 15, 2014 https://doi.org/10.3892/or.2014.3186
Pages: 395-402

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colon cancer is one of the most frequently diagnosed cancer and the third most fatal malignancy worldwide. HOTAIR, a cancer-associated long non-coding RNA (lncRNA), is a powerful biomarker of metastasis and poor prognosis in a diverse group of cancers. Nevertheless, an understanding of how HOTAIR is involved in colon cancer progression is limited. In the present study, we hypothesized that HOTAIR plays a crucial role in colon cancer development. We evaluated the expression of HOTAIR in 120 colon cancer samples, matched adjacent non-tumor mucosa and 32 lymph node metastasis tissues by real-time PCR. Increased HOTAIR expression was significantly correlated with the depth of tumor invasion, lymph node metastasis, organ metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with high HOTAIR expression had higher recurrence rates and reduced metastasis-free and overall survival than patients with low HOTAIR expression. Moreover, our findings revealed that HOTAIR had a limited effect on cell proliferation but significantly promoted colon cancer cell migration and invasion in vitro. Depletion of HOTAIR increased the expression of E-cadherin while concomitantly decreasing expression of vimentin and MMP9. Hence, HOTAIR may be another pleiotropic modulator participating in epithelial-mesenchymal transition (EMT). These results indicate that HOTAIR may also be a valuable predictor for colon cancer management; furthermore, this lncRNA may be a potential target for cancer prevention and treatment.

View Figures

View References

1	NCCN Clinical Practice Guidelines in Oncology for Colon Cancer (Version 3). 2013, [EB/OL] Available at www.nccn.org/professionals/physician_gls/f_guidelines.asp.
2	Li M and Gu J: Changing patterns of colorectal cancer in China over a period of 20 years. World J Gastroenterol. 11:4685–4688. 2005.PubMed/NCBI
3	Fearon ER: Molecular genetics of colorectal cancer. Annu Rev Pathol. 6:479–507. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ulitsky I and Bartel DP: lincRNAs: genomics, evolution, and mechanisms. Cell. 154:26–46. 2013. View Article : Google Scholar
5	Gupta RA, Shah N, Wang KC, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010.PubMed/NCBI
6	Yang Z, Zhou L, Wu LM, et al: Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 18:1243–1250. 2011. View Article : Google Scholar : PubMed/NCBI
7	Lu L, Zhu G, Zhang C, 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. 136:875–883. 2012. View Article : Google Scholar : PubMed/NCBI
8	Niinuma T, Suzuki H, Nojima M, et al: Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 72:1126–1136. 2012.PubMed/NCBI
9	Kim K, Jutooru I, Chadalapaka G, et al: HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 32:1616–1625. 2013. View Article : Google Scholar : PubMed/NCBI
10	Li D, Feng J, Wu T, et al: Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am J Pathol. 182:64–70. 2013. View Article : Google Scholar
11	Nakagawa T, Endo H, Yokoyama M, et al: Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun. 436:319–324. 2013. View Article : Google Scholar
12	Zhuang Y, Wang X, Nguyen HT, et al: Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol. 6:352013. View Article : Google Scholar : PubMed/NCBI
13	Kogo R, Shimamura T, Mimori K, et al: Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 71:6320–6326. 2011.PubMed/NCBI
14	Rinn JL, Kertesz M, Wang JK, et al: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 129:1311–1323. 2007. View Article : Google Scholar : PubMed/NCBI
15	Tsai MC, Manor O, Wan Y, et al: Long noncoding RNA as modular scaffold of histone modification complexes. Science. 329:689–693. 2010. View Article : Google Scholar : PubMed/NCBI
16	Sparmann A and van Lohuizen M: Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer. 6:846–856. 2006. View Article : Google Scholar : PubMed/NCBI
17	Richly H, Aloia L and Di Croce L: Roles of the Polycomb group proteins in stem cells and cancer. Cell Death Dis. 2:e2042011. View Article : Google Scholar : PubMed/NCBI
18	Crea F, Fornaro L, Bocci G, et al: EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer Metastasis Rev. 31:753–761. 2012. View Article : Google Scholar : PubMed/NCBI
19	Ding J, Zhang ZM, Xia Y, et al: LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer. Br J Cancer. 109:994–1003. 2013. View Article : Google Scholar : PubMed/NCBI
20	Huang Z, Li S, Song W, et al: Lysine-specific demethylase 1 (LSD1/KDM1A) contributes to colorectal tumorigenesis via activation of the Wnt/β-catenin pathway by down-regulating Dickkopf-1 (DKK1). PLoS One. 8:e700772013.PubMed/NCBI
21	Tang M, Shen H, Jin Y, et al: The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition. J Biol Chem. 288:27680–27691. 2013. View Article : Google Scholar
22	Abdel-Wahab O and Dey A: The ASXL-BAP1 axis: new factors in myelopoiesis, cancer and epigenetics. Leukemia. 27:10–15. 2013. View Article : Google Scholar : PubMed/NCBI
23	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI