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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression

Authors: Yongguo Shi, Juan Li, Yangchen Liu, Jie Ding, Yingrui Fan, Yun Tian, Li Wang, Yifan Lian, Keming Wang, Yongqian Shu

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear.

Methods

Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR.

Results

SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (−) breast carcinoma cells.

Conclusions

SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.
Appendix
Available only for authorised users
Literature
1.
Gerasimova E, Audit B, Roux SG, Khalil A, Gileva O, Argoul F, et al. Wavelet-based multifractal analysis of dynamic infrared thermograms to assist in early breast cancer diagnosis. Front Physiol. 2014;5:176.CrossRefPubMedCentralPubMed
2.
Molloy TJ, Devriese LA, Helgason HH, Bosma AJ, Hauptmann M, Voest EE, et al. A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer. Br J Cancer. 2011;104:1913–9.CrossRefPubMedCentralPubMed
3.
Ambrogi F, Biganzoli E, Querzoli P, Ferretti S, Boracchi P, Alberti S, et al. Molecular subtyping of breast cancer from traditional tumor marker profiles using parallel clustering methods. Clin Cancer Res. 2006;12:781–90.CrossRefPubMed
4.
Bosma AJ, Weigelt B, Lambrechts AC, Verhagen OJ, Pruntel R, Hart AA, et al. Detection of circulating breast tumor cells by differential expression of marker genes. Clin Cancer Res. 2002;8:1871–7.PubMed
5.
6.
7.
Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477:295–300.CrossRefPubMedCentralPubMed
8.
9.
Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat. 2014;145:359–70.CrossRefPubMed
10.
11.
12.
13.
14.
Shore AN, Herschkowitz JI, Rosen JM. Noncoding RNAs involved in mammary gland development and tumorigenesis: there's a long way to go. J Mammary Gland Biol Neoplasia. 2012;17:43–58.CrossRefPubMedCentralPubMed
15.
Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28:195–208.CrossRefPubMed
16.
Mourtada-Maarabouni M, Hasan AM, Farzaneh F, Williams GT. Inhibition of human T-cell proliferation by mammalian target of rapamycin (mTOR) antagonists requires noncoding RNA growth-arrest-specific transcript 5 (GAS5). Mol Pharmacol. 2010;78:19–28.CrossRefPubMedCentralPubMed
17.
Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F, Williams GT. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci. 2008;121:939–46.CrossRefPubMed
18.
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;464:1071–6.CrossRefPubMedCentralPubMed
19.
Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446:448–53.CrossRefPubMed
20.
Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 2011;71:3852–62.CrossRefPubMed
21.
Zou Y, Jiang Z, Yu X, Sun M, Zhang Y, Zuo Q, et al. Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. PLoS One. 2013;8:e79598.CrossRefPubMedCentralPubMed
22.
Holland DG, Burleigh A, Git A, Goldgraben MA, Perez-Mancera PA, Chin SF, et al. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med. 2011;3:167–80.CrossRefPubMedCentralPubMed
23.
Sircoulomb F, Nicolas N, Ferrari A, Finetti P, Bekhouche I, Rousselet E, et al. ZNF703 gene amplification at 8p12 specifies luminal B breast cancer. EMBO Mol Med. 2011;3:153–66.CrossRefPubMedCentralPubMed
24.
25.
Ginestier C, Sircoulomb F, Charafe-Jauffret E, Chaffanet M, Birnbaum D. [ZNF703: a novel oncogene involved in breast cancer]. Med Sci (Paris). 2011;27:357–9.CrossRef
26.
Melchor L, Garcia MJ, Honrado E, Pole JC, Alvarez S, Edwards PA, et al. Genomic analysis of the 8p11-12 amplicon in familial breast cancer. Int J Cancer. 2007;120:714–7.CrossRefPubMed
27.
Slorach EM, Chou J, Werb Z. Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization. Genes Dev. 2011;25:471–84.CrossRefPubMedCentralPubMed
28.
Reynisdottir I, Arason A, Einarsdottir BO, Gunnarsson H, Staaf J, Vallon-Christersson J, et al. High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer. Cancer Med. 2013;2:437–46.CrossRefPubMedCentralPubMed
29.
30.
Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458:223–7.CrossRefPubMedCentralPubMed
31.
32.
Ponjavic J, Ponting CP, Lunter G. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res. 2007;17:556–65.CrossRefPubMedCentralPubMed
33.
34.
Sun M, Liu XH, Lu KH, Nie FQ, Xia R, Kong R, et al. EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis. 2014;5:e1298.CrossRefPubMed
35.
Xie HW, Wu QQ, Zhu B, Chen FJ, Ji L, Li SQ, et al. Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis. Tumour Biol. 2014;35:7743–54.CrossRefPubMed
Metadata
Title
The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression
Authors
Yongguo Shi
Juan Li
Yangchen Liu
Jie Ding
Yingrui Fan
Yun Tian
Li Wang
Yifan Lian
Keming Wang
Yongqian Shu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0318-0

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