Forkhead box C1 promoter upstream transcript, a novel long non-coding RNA, regulates proliferation and migration in basal-like breast cancer

Liu,Juntao; Shen,Lei; Yao,Jie; Li,Yi; Wang,Yongcheng; Chen,Hong; Geng,Peiliang

doi:10.3892/mmr.2014.3089

Forkhead box C1 promoter upstream transcript, a novel long non-coding RNA, regulates proliferation and migration in basal-like breast cancer

Authors:
- Juntao Liu
- Lei Shen
- Jie Yao
- Yi Li
- Yongcheng Wang
- Hong Chen
- Peiliang Geng
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Affiliations: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, P.R. China, Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Oncology, PLA Center Hospital, Wuhan, Hubei 430000, P.R. China, Oncology Department, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital, Beijing 100853, P.R. China, Orthopedics Department, Institute of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Oncology, Kunming General Hospital of Chendu Military Command, Kunming, Yunnan 650032, P.R. China
Published online on: December 15, 2014 https://doi.org/10.3892/mmr.2014.3089
Pages: 3155-3159

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Abstract

Recent studies have shown that long non‑coding RNAs (lncRNAs) have crucial regulating roles in carcinogenesis. Forkhead box C1 (FOXC1) is an important cancer‑associated gene in basal‑like breast cancer (BLBC). In the present study, a novel lncRNA, FOXC1 promoter upstream transcript (FOXCUT) was investigated in BLBC patients using polymerase chain reaction analysis. The results showed that the expression of FOXCUT and FOXC1 were positively correlated. When the expression of FOXCUT was downregulated by small interfering RNA, the expression of FOXC1 was similarly reduced. Furthermore, in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells, knockdown of FOXCUT markedly inhibited cell proliferation and migration in vitro. In conclusion, FOXCUT lncRNA may be functionally involved in the tumor progression of BLBCs through the regulation of its paired mRNA, FOXC1, demonstrating that FOXCUT may serve as a novel biomarker and therapeutic target in BLBCs.

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1	Kreike B, van Kouwenhove M, Horlings H, et al: Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res. 9:R652007. View Article : Google Scholar : PubMed/NCBI
2	Rakha EA, Reis-Filho JS and Ellis IO: Basal-like breast cancer: a critical review. J Clin Oncol. 26:2568–2581. 2008. View Article : Google Scholar : PubMed/NCBI
3	Carey LA, Perou CM, Livasy CA, et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295:2492–2502. 2006. View Article : Google Scholar : PubMed/NCBI
4	Huarte M and Rinn JL: Large non-coding RNAs: missing links in cancer? Hum Mol Genet. 19:R152–R161. 2010. View Article : Google Scholar : PubMed/NCBI
5	Spizzo R, Almeida MI, Colombatti A and Calin GA: Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 31:4577–4587. 2012. View Article : Google Scholar : PubMed/NCBI
6	Tsai MC, Spitale RC and Chang HY: Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 71:3–7. 2011. View Article : Google Scholar : PubMed/NCBI
7	Okazaki Y, Furuno M, Kasukawa T, et al: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 420:563–573. 2002. View Article : Google Scholar : PubMed/NCBI
8	Guttman M, Amit I, Garber M, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI
9	Perez DS, Hoage TR, Pritchett JR, et al: Long, abundantly expressed non-coding transcripts are altered in cancer. Hum Mol Genet. 17:642–655. 2008. View Article : Google Scholar
10	Han L, Zhang K, Shi Z, et al: LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. Int J Oncol. 40:2004–2012. 2012.PubMed/NCBI
11	Myatt SS and Lam EW: The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer. 7:847–859. 2007. View Article : Google Scholar : PubMed/NCBI
12	Xia L, Huang W, Tian D, et al: Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma. Hepatology. 57:610–624. 2013. View Article : Google Scholar
13	Xu ZY, Ding SM, Zhou L, et al: FOXC1 contributes to microvascular invasion in primary hepatocellular carcinoma via regulating epithelial-mesenchymal transition. Int J Biol Sci. 8:1130–1141. 2012. View Article : Google Scholar : PubMed/NCBI
14	Sizemore ST and Keri RA: The forkhead box transcription factor FOXC1 promotes breast cancer invasion by inducing matrix metalloprotease 7 (MMP7) expression. J Biol Chem. 287:24631–24640. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ray PS, Wang J, Qu Y, et al: FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Res. 70:3870–3876. 2010. View Article : Google Scholar : PubMed/NCBI
16	Ray PS, Bagaria SP, Wang J, et al: Basal-like breast cancer defined by FOXC1 expression offers superior prognostic value: a retrospective immunohistochemical study. Ann Surg Oncol. 18:3839–3847. 2011. View Article : Google Scholar : PubMed/NCBI
17	Wang L, Gu F, Liu CY, Wang RJ, Li J and Xu JY: High level of FOXC1 expression is associated with poor prognosis in pancreatic ductal adenocarcinoma. Tumour Biol. 34:853–858. 2013. View Article : Google Scholar
18	Wei LX, Zhou RS, Xu HF, Wang JY and Yuan MH: High expression of FOXC1 is associated with poor clinical outcome in non-small cell lung cancer patients. Tumour Biol. 34:941–946. 2013. View Article : Google Scholar
19	Livasy CA, Karaca G, Nanda R, et al: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 19:264–271. 2006. View Article : Google Scholar
20	Nielsen TO, Hsu FD, Jensen K, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 10:5367–5374. 2004. View Article : Google Scholar : PubMed/NCBI
21	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. View Article : Google Scholar : PubMed/NCBI
22	Iacoangeli A, Lin Y, Morley EJ, et al: BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis. 25:2125–2133. 2004. View Article : Google Scholar : PubMed/NCBI
23	Redis RS, Sieuwerts AM, Look MP, et al: CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations. Oncotarget. 4:1748–1762. 2013.PubMed/NCBI
24	Shtivelman E and Bishop JM: Effects of translocations on transcription from PVT. Mol Cell Biol. 10:1835–1839. 1990.PubMed/NCBI
25	Guan Y, Kuo WL, Stilwell JL, et al: Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer. Clin Cancer Res. 13:5745–5755. 2007. View Article : Google Scholar : PubMed/NCBI
26	Preker P, Nielsen J, Kammler S, et al: RNA exosome depletion reveals transcription upstream of active human promoters. Science. 322:1851–1854. 2008. View Article : Google Scholar : PubMed/NCBI
27	Jacquier A: The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet. 10:833–844. 2009. View Article : Google Scholar : PubMed/NCBI
28	Preker P, Almvig K, Christensen MS, et al: PROMoter uPstream Transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters. Nucleic Acids Res. 39:7179–7193. 2011. View Article : Google Scholar : PubMed/NCBI