Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method

Wang,Xinmei; Li,Mingyue; Yin,Yingchun; Li,Liang; Tao,Yuqian; Chen,Dengguo; Li,Jianzhao; Han,Hongmei; Hou,Zhenbo; Zhang,Baohua; Wang,Xinyun; Ding,Yu; Cui,Haiyan; Zhang,Hengming

doi:10.3892/ijmm.2014.1973

Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method

Authors:
- Xinmei Wang
- Mingyue Li
- Yingchun Yin
- Liang Li
- Yuqian Tao
- Dengguo Chen
- Jianzhao Li
- Hongmei Han
- Zhenbo Hou
- Baohua Zhang
- Xinyun Wang
- Yu Ding
- Haiyan Cui
- Hengming Zhang
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Affiliations: Department of Pathology, The Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China, Department of Neurology, The First Affiliated Hospital of Zhongshan University, Guangzhou, Guangdong 510080, P.R. China, Department of Breast and Thyroid Surgery, The Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China, Department of Neurology, The Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China
Published online on: October 20, 2014 https://doi.org/10.3892/ijmm.2014.1973
Pages: 39-50
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Breast cancer (BC) is a leading cause of cancer-related mortality in females and is recognized as a molecularly heterogeneous disease. Previous studies have suggested that alternative messenger RNA (mRNA) processing, particularly alternative polyadenylation [poly(A)] (APA), can be a powerful molecular biomarker with prognostic potential. Therefore, in the present study, we profiled APA sites in the luminal B subtype of BC by sequencing APA sites (SAPAS) method, in order to assess the relation of these APA site-switching events to the recognized molecular subtypes of BC, and to discover novel candidate genes and pathways in BC. Through comprehensive analysis, the trend of APA site-switching events in the 3' untranslated regions (3'UTRs) in the luminal B subtype of BC were found to be the same as that in MCF7 cell lines. Among the genes involved in the events, a significantly greater number of genes was found with shortened 3'UTRs in the samples, which were samples of primary cancer with relatively low proliferation. These findings may provide novel information for the clinical diagnosis and prognosis on a molecular level. Several potential biomarkers with significantly differential tandem 3'UTRs and expression were found and validated. The related biological progresses and pathways involved were partly confirmed by other studies. In conclusion, this study provides new insight into the diagnosis and prognosis of BC from the APA site profile aspect.

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1	Sørlie T, Perou CM, Tibshirani R, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 98:10869–10874. 2001. View Article : Google Scholar : PubMed/NCBI
2	Sorlie T, Tibshirani R, Parker J, et al: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 100:8418–8423. 2003. View Article : Google Scholar : PubMed/NCBI
3	Kao J, Salari K, Bocanegra M, et al: Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One. 4:e61462009. View Article : Google Scholar : PubMed/NCBI
4	Tran B and Bedard PL: Luminal-B breast cancer and novel therapeutic targets. Breast Cancer Res. 13:2212011. View Article : Google Scholar
5	Cadoo KA, Fornier MN and Morris PG: Biological subtypes of breast cancer: current concepts and implications for recurrence patterns. Q J Nucl Med Mol Imaging. 57:312–321. 2013.PubMed/NCBI
6	Rouzier R, Perou CM, Symmans WF, et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 11:5678–5685. 2005. View Article : Google Scholar : PubMed/NCBI
7	Sandberg R, Neilson JR, Sarma A, Sharp PA and Burge CB: Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science. 320:1643–1647. 2008. View Article : Google Scholar : PubMed/NCBI
8	Mayr C and Bartel DP: Widespread shortening of 3′UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 138:673–684. 2009. View Article : Google Scholar : PubMed/NCBI
9	Vlasova IA, Tahoe NM, Fan D, et al: Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell. 29:263–270. 2008. View Article : Google Scholar : PubMed/NCBI
10	Tian B, Hu J, Zhang H and Lutz CS: A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res. 33:201–212. 2005. View Article : Google Scholar : PubMed/NCBI
11	Wang ET, Sandberg R, Luo S, et al: Alternative isoform regulation in human tissue transcriptomes. Nature. 456:470–476. 2008. View Article : Google Scholar : PubMed/NCBI
12	Pickrell JK, Marioni JC, Pai AA, et al: Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature. 464:768–772. 2010. View Article : Google Scholar : PubMed/NCBI
13	Mangone M, Manoharan AP, Thierry-Mieg D, et al: The landscape of C. elegans 3′UTRs. Science. 329:432–435. 2010. View Article : Google Scholar : PubMed/NCBI
14	Jan CH, Friedman RC, Ruby JG and Bartel DP: Formation, regulation and evolution of Caenorhabditis elegans 3′UTRs. Nature. 469:97–101. 2011. View Article : Google Scholar :
15	Fu Y, Sun Y, Li Y, Rao X, Chen C and Xu A: Differential genome-wide profiling of tandem 3′ UTRs among human breast cancer and normal cells by high-throughput sequencing. Genome Res. 21:741–747. 2011. View Article : Google Scholar : PubMed/NCBI
16	Ozsolak F, Kapranov P, Foissac S, et al: Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation. Cell. 143:1018–1029. 2010. View Article : Google Scholar : PubMed/NCBI
17	Subtelny AO, Eichhorn SW, Chen GR, Sive H and Bartel DP: Poly(A)-tail profiling reveals an embryonic switch in translational control. Nature. 508:66–71. 2014. View Article : Google Scholar : PubMed/NCBI
18	Sun Y, Fu Y, Li Y and Xu A: Genome-wide alternative polyadenylation in animals: insights from high-throughput technologies. J Mol Cell Biol. 4:352–361. 2012. View Article : Google Scholar : PubMed/NCBI
19	Rhead B, Karolchik D, Kuhn RM, et al: The UCSC Genome Browser database: update 2010. Nucleic Acids Res. 38:D613–D619. 2010. View Article : Google Scholar :
20	Langmead B: Aligning short sequencing reads with Bowtie. Curr Protoc Bioinformatics. Chapter 11(Unit 11.7)2010. View Article : Google Scholar : PubMed/NCBI
21	Tian P, Sun Y, Li Y, et al: A global analysis of tandem 3′UTRs in eosinophilic chronic rhinosinusitis with nasal polyps. PLoS One. 7:e489972012. View Article : Google Scholar
22	Lee JY, Yeh I, Park JY and Tian B: PolyA_DB 2: mRNA polyadenylation sites in vertebrate genes. Nucleic Acids Res. 35:D165–D168. 2007. View Article : Google Scholar : PubMed/NCBI
23	Sun M, Ju H, Zhou Z and Zhu R: Pilot genome-wide study of tandem 3′UTRs in esophageal cancer using high-throughput sequencing. Mol Med Rep. 9:1597–1605. 2014.PubMed/NCBI
24	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar :
25	Kimbung S, Biskup E, Johansson I, et al: Co-targeting of the PI3K pathway improves the response of BRCA1 deficient breast cancer cells to PARP1 inhibition. Cancer Lett. 319:232–241. 2012. View Article : Google Scholar : PubMed/NCBI
26	Lei H, Hemminki K, Altieri A, et al: Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression. Breast Cancer Res Treat. 103:61–69. 2007. View Article : Google Scholar
27	Han X, Zhang H, Jia M, Han G and Jiang W: Expression of TIMP-3 gene by construction of a eukaryotic cell expression vector and its role in reduction of metastasis in a human breast cancer cell line. Cell Mol Immunol. 1:308–310. 2004.
28	Chen D, Xu W, Bales E, et al: SKI activates Wnt/beta-catenin signaling in human melanoma. Cancer Res. 63:6626–6634. 2003.PubMed/NCBI
29	Sánchez-Velar N, Udofia EB, Yu Z and Zapp ML: hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 18:23–34. 2004. View Article : Google Scholar : PubMed/NCBI
30	Lévesque K, Halvorsen M, Abrahamyan L, et al: Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly. Traffic. 7:1177–1193. 2006. View Article : Google Scholar : PubMed/NCBI
31	Varadarajan P, Mahalingam S, Liu P, et al: The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr. Mol Biol Cell. 16:1823–1838. 2005. View Article : Google Scholar : PubMed/NCBI
32	Radvanyi L, Singh-Sandhu D, Gallichan S, et al: The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer. Proc Natl Acad Sci USA. 102:11005–11010. 2005. View Article : Google Scholar : PubMed/NCBI
33	Zhang WJ, Li BH, Yang XZ, et al: IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells. Cytokine. 42:39–47. 2008. View Article : Google Scholar : PubMed/NCBI
34	He Q, Zhang SQ, Chu YL, Jia XL and Wang XL: The correlations between HPV16 infection and expressions of c-erbB-2 and bcl-2 in breast carcinoma. Mol Biol Rep. 36:807–812. 2009. View Article : Google Scholar
35	Fernández Y, Gu B, Martínez A, Torregrosa A and Sierra A: Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state. Int J Cancer. 101:317–326. 2002. View Article : Google Scholar : PubMed/NCBI
36	Tsutsui S, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, Higashi H and Era S: Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer. BMC Cancer. 6:1872006. View Article : Google Scholar : PubMed/NCBI
37	Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM and Fernandez-Luna JL: Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene. 21:7611–7618. 2002. View Article : Google Scholar : PubMed/NCBI
38	Neri A, Marrelli D, Roviello F, et al: Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer. Breast Cancer Res Treat. 99:77–83. 2006. View Article : Google Scholar : PubMed/NCBI
39	Tokunaga E, Oki E, Kimura Y, et al: Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma. Breast Cancer Res Treat. 101:249–257. 2007. View Article : Google Scholar
40	Palmieri D, Astigiano S, Barbieri O, et al: Procollagen I COOH-terminal fragment induces VEGF-A and CXCR4 expression in breast carcinoma cells. Exp Cell Res. 314:2289–2298. 2008. View Article : Google Scholar : PubMed/NCBI
41	Holliday DL and Speirs V: Choosing the right cell line for breast cancer research. Breast Cancer Res. 13:2152011. View Article : Google Scholar : PubMed/NCBI
42	Perou CM, Sørlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI
43	Singh P, Alley TL, Wright SM, et al: Global changes in processing of mRNA 3′ untranslated regions characterize clinically distinct cancer subtypes. Cancer Res. 69:9422–9430. 2009. View Article : Google Scholar : PubMed/NCBI
44	Ji Z, Lee JY, Pan Z, Jiang B and Tian B: Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc Natl Acad Sci USA. 106:7028–7033. 2009. View Article : Google Scholar
45	Daemen A, Griffith OL, Heiser LM, et al: Modeling precision treatment of breast cancer. Genome Biol. 14:R1102013. View Article : Google Scholar : PubMed/NCBI
46	Schlange T, Matsuda Y, Lienhard S, Huber A and Hynes NE: Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation. Breast Cancer Res. 9:R632007. View Article : Google Scholar : PubMed/NCBI
47	Lamb R, Ablett MP, Spence K, Landberg G, Sims AH and Clarke RB: Wnt Pathway activity in breast cancer sub-types and stem-like cells. PLoS One. 8:e678112013. View Article : Google Scholar : PubMed/NCBI
48	Lu J, Wen M, Huang Y, et al: C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes. Epigenetics. 8:571–583. 2013. View Article : Google Scholar : PubMed/NCBI
49	Sathya S, Sudhagar S, Sarathkumar B and Lakshmi BS: EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells. Life Sci. 95:53–62. 2014. View Article : Google Scholar
50	Clancy J and McVicar A: Homeostasis 5: nurses as external agents of control in breast cancer. Br J Nurs. 20:426428–430. 432–437. 2011. View Article : Google Scholar : PubMed/NCBI
51	Zhang BH, Liu J, Zhou QX, Zuo D and Wang Y: Analysis of differentially expressed genes in ductal carcinoma with DNA microarray. Eur Rev Med Pharmacol Sci. 17:758–766. 2013.PubMed/NCBI