Long non-coding RNA HOXD-AS1 promotes tumor progression and predicts poor prognosis in colorectal cancer

Li,Xiang; Zhao,Xinhan; Yang,Binhui; Li,Yuqing; Liu,Tao; Pang,Linyuan; Fan,Zhigang; Ma,Wu; Liu,Zhongqiu; Li,Zeng

doi:10.3892/ijo.2018.4400

Long non-coding RNA HOXD-AS1 promotes tumor progression and predicts poor prognosis in colorectal cancer

Authors:
- Xiang Li
- Xinhan Zhao
- Binhui Yang
- Yuqing Li
- Tao Liu
- Linyuan Pang
- Zhigang Fan
- Wu Ma
- Zhongqiu Liu
- Zeng Li
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Affiliations: Department of Second Medical Oncology, The Affiliated 3201 Hospital of Xi'an Jiaotong University, Hanzhong, Shaanxi 723000, P.R. China
Published online on: May 9, 2018 https://doi.org/10.3892/ijo.2018.4400
Pages: 21-32
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mounting evidence has indicated that long non‑coding RNAs (lncRNA) serve important roles in tumor development. Previous studies have demonstrated that the lncRNA HOXD cluster antisense RNA 1 (HOXD‑AS1) promotes tumor progression in numerous types of cancer; however, the role of HOXD‑AS1 in colorectal cancer (CRC) remains unclear. In the present study, the expression levels of HOXD‑AS1 were detected in CRC tissues and cell lines using quantitative polymerase chain reaction. In addition, the biological effects of HOXD‑AS1 on CRC were evaluated in vitro by cell counting kit‑8, colony formation and Transwell assays, and in vivo by tumorigenesis and metastasis assays. The results demonstrated that HOXD‑AS1 was upregulated in CRC tissues and cell lines, and that overexpression of HOXD‑AS1 was associated with poor prognosis in patients with CRC. Furthermore, knockdown of HOXD‑AS1 inhibited cell proliferation, cell invasion, epithelial‑mesenchymal transition and stem cell formation in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, HOXD‑AS1 functioned as a competing endogenous RNA for miR‑217. In conclusion, the present study demonstrated that HOXD‑AS1 may promote CRC progression and metastasis by competing for miR‑217. In addition, HOXD‑AS1 may be considered an indicator of prognosis in patients with CRC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Goldstein DA, Zeichner SB, Bartnik CM, Neustadter E and Flowers CR: Metastatic Colorectal Cancer: A Systematic Review of the Value of Current Therapies. Clin Colorectal Cancer. 15:1–6. 2016. View Article : Google Scholar :
3	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
5	Rinn JL and Chang HY: Genome regulation by long noncoding RNAs. Annu Rev Biochem. 81:145–166. 2012. View Article : Google Scholar : PubMed/NCBI
6	Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E and Chang HY: Long noncoding RNA as modular scaffold of histone modification complexes. Science. 329:689–693. 2010. View Article : Google Scholar : PubMed/NCBI
7	Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, et al: A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 472:120–124. 2011. View Article : Google Scholar : PubMed/NCBI
8	Graham A, Papalopulu N and Krumlauf R: The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 57:367–378. 1989. View Article : Google Scholar : PubMed/NCBI
9	Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, 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
10	Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, Deng X, Jin H, Wang N, Wang C, et al: STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 16:1362017. View Article : Google Scholar : PubMed/NCBI
11	Gu P, Chen X, Xie R, Han J, Xie W, Wang B, Dong W, Chen C, Yang M, Jiang J, et al: lncRNA HOXD-AS1 regulates proliferation and chemo-resistance of castration-resistant prostate cancer via recruiting WDR5. Mol Ther. 25:1959–1973. 2017. View Article : Google Scholar : PubMed/NCBI
12	Li J, Zhuang C, Liu Y, Chen M, Chen Y, Chen Z, He A, Lin J, Zhan Y, Liu L, et al: Synthetic tetracycline-controllable shRNA targeting long non-coding RNA HOXD-AS1 inhibits the progression of bladder cancer. J Exp Clin Cancer Res. 35:992016. View Article : Google Scholar : PubMed/NCBI
13	Lu S, Zhou J, Sun Y, Li N, Miao M, Jiao B and Chen H: The noncoding RNA HOXD-AS1 is a critical regulator of the metastasis and apoptosis phenotype in human hepatocellular carcinoma. Mol Cancer. 16:1252017. View Article : Google Scholar : PubMed/NCBI
14	Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM and Chen J: The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 31:1726–1733. 2010. View Article : Google Scholar : PubMed/NCBI
15	Zhang JX, Chen ZH, Xu Y, Chen JW, Weng HW, Yun M, Zheng ZS, Chen C, Wu BL and Li EM: Downregulation of MicroRNA-644a promotes esophageal squamous cell carcinoma aggressiveness and stem cell-like phenotype via dysregulation of ITX2. Clin Cancer Res. 23:298–310. 2017. View Article : Google Scholar
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
17	Lu YX, Ju HQ, Wang F, Chen LZ, Wu QN, Sheng H, Mo HY, Pan ZZ, Xie D, Kang TB, et al: Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis. Cancer Lett. 380:87–97. 2016. View Article : Google Scholar : PubMed/NCBI
18	Chen DL, Ju HQ, Lu YX, Chen LZ, Zeng ZL, Zhang DS, Luo HY, Wang F, Qiu MZ, Wang DS, et al: Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression. J Exp Clin Cancer Res. 35:1422016. View Article : Google Scholar : PubMed/NCBI
19	Teng KY, Qiu MZ, Li ZH, Luo HY, Zeng ZL, Luo RZ, Zhang HZ, Wang ZQ, Li YH and Xu RH: DNA polymerase η protein expression predicts treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy. J Transl Med. 8:1262010. View Article : Google Scholar
20	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
21	Chen T, You Y, Jiang H and Wang ZZ: Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 232:3261–3272. 2017. View Article : Google Scholar : PubMed/NCBI
22	Jiang C, Li X, Zhao H and Liu H: Long non-coding RNAs: Potential new biomarkers for predicting tumor invasion and metastasis. Mol Cancer. 15:622016. View Article : Google Scholar : PubMed/NCBI
23	Ulitsky I and Bartel DP: lincRNAs: Genomics, evolution, and mechanisms. Cell. 154:26–46. 2013. View Article : Google Scholar : PubMed/NCBI
24	Ma Y, Yang Y, Wang F, Moyer MP, Wei Q, Zhang P, Yang Z, Liu W, Zhang H, Chen N, et al: Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/β-catenin signalling pathway via suppression of activator protein 2α. Gut. 65:1494–1504. 2016. View Article : Google Scholar
25	Chen DL, Chen LZ, Lu YX, Zhang DS, Zeng ZL, Pan ZZ, Huang P, Wang FH, Li YH, Ju HQ, et al: Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer. Cell Death Dis. 8:e30112017. View Article : Google Scholar : PubMed/NCBI
26	Zheng L, Chen J, Zhou Z and He Z: Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway. Tumour Biol. 39:10104283177053352017. View Article : Google Scholar : PubMed/NCBI
27	Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A and Bozzoni I: A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 147:358–369. 2011. View Article : Google Scholar : PubMed/NCBI
28	Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, Chen N, Sun F and Fan Q: CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 38:5366–5383. 2010. View Article : Google Scholar : PubMed/NCBI
29	Zhou W, Ye XL, Xu J, Cao MG, Fang ZY, Li LY, Guan GH, Liu Q, Qian YH and Xie D: The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b. Sci Signal. 10:102017. View Article : Google Scholar
30	Wang B, Shen ZL, Jiang KW, Zhao G, Wang CY, Yan YC, Yang Y, Zhang JZ, Shen C, Gao ZD, et al: MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism. BMC Cancer. 15:4372015. View Article : Google Scholar : PubMed/NCBI
31	Flum M, Kleemann M, Schneider H, Weis B, Fischer S, Handrick R and Otte K: miR-217-5p induces apoptosis by directly targeting PRKCI, BAG3, ITGAV and MAPK1 in colorectal cancer cells. J Cell Commun Signal. Sep 14–2017.Epub ahead of print. PubMed/NCBI
32	Liu YP, Sun XH, Cao XL, Jiang WW, Wang XX, Zhang YF and Wang JL: MicroRNA-217 suppressed epithelial-to-mesenchymal transition in gastric cancer metastasis through targeting PTPN14. Eur Rev Med Pharmacol Sci. 21:1759–1767. 2017.PubMed/NCBI
33	Lu L, Luo F, Liu Y, Liu X, Shi L, Lu X and Liu Q: Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial-mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Appl Pharmacol. 289:276–285. 2015. View Article : Google Scholar : PubMed/NCBI
34	Deng S, Zhu S, Wang B, Li X, Liu Y, Qin Q, Gong Q, Niu Y, Xiang C, Chen J, et al: Chronic pancreatitis and pancreatic cancer demonstrate active epithelial-mesenchymal transition profile, regulated by miR-217-SIRT1 pathway. Cancer Lett. 355:184–191. 2014. View Article : Google Scholar : PubMed/NCBI
35	Miao S, Mao X, Zhao S, Song K, Xiang C, Lv Y, Jiang H, Wang L, Li B, Yang X, et al: miR-217 inhibits laryngeal cancer metastasis by repressing AEG-1 and PD-L1 expression. Oncotarget. 8:62143–62153. 2017. View Article : Google Scholar : PubMed/NCBI
36	Chen DL, Zhang DS, Lu YX, Chen LZ, Zeng ZL, He MM, Wang FH, Li YH, Zhang HZ, Pelicano H, et al: microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer. Oncotarget. 6:10868–10879. 2015.PubMed/NCBI