Construction and functional analysis of circular RNA interaction network based on open chromatin in breast cancer

doi:10.3969/j.issn.1006-7795.2019.06.017

Abstract

Abstract: Objective To identify some important circular RNAs (circRNAs) in breast cancer and the molecular biological processes in which they participate. Methods Genome-wide analysis of three breast cancer cell lines:Dnase Ⅰ hypersensitive sites sequencing data (DNase-seq) and assay for transposase accessible chromatin with high-throughput sequencing data, (ATAC-seq) of MCF-7, T-47D, MDA-MB-231,and screening out the corresponding activated circRNA on the sequence of the captured gene encoding were done. Then the activated circRNA gene was enriched and screened based on KEGG pathway. In this result, the activated circRNA gene shared in three cell lines was selected, and the interaction network of activated circRNA gene in breast cancer was constructed according to the molecular biological process of Gene Ontology. Results The expression regulatory network identified 111 key functional modules, which were mainly divided into regulation and response categories, and included some important signaling pathways. In the active circRNA gene interaction network, the activated circRNA gene with connectivity greater than 50 was defined as hub gene, and the corresponding circRNA of hub gene was defined as hub circRNA, including PTK2B, PDCD6IP, ABL1, EGFR, RHOA, MTOR, NRP1, ATR, CTNNB1, ILK, NF1, PRKCA, HNRNPK, MEF2C, PMAIP1, LYN, NR4A3, SRF, AREG, PML, PTK2, ROCK2, TGFBR2, VEGFA, DLG1, HRAS, ITGA2, CREB1, STAT3, RUNX2 and TIAM1.Conclusion Activated circRNA in the chromatin of breast cancer cells is mainly involved in positive and negative regulation of cell cycle, apoptosis, proliferation, differentiation and other important cellular biological processes, which indicates that circRNA plays an important role in the occurrence and development of breast cancer.

Key words: breast cancer, circular RNA, open chromatin localization, high throughput sequencing, circRNA interaction network

CLC Number:

Zhang Yunxian, Wang Yamei, Zhou Ping. Construction and functional analysis of circular RNA interaction network based on open chromatin in breast cancer[J]. Journal of Capital Medical University, 2019, 40(6): 901-910.

0
/ Save 0 / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.06.017

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I6/901

References

[1] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1):7-30.
[2] Guo Y, Warren Andersen S, Shu X O, et al. Genetically predicted body mass index and breast cancer risk:mendelian randomization analyses of data from 145,000 women of european descent[J]. PLoS Med, 2016, 13(8):e1002105.
[3] Chlebowski R T, Manson J E, Anderson G L, et al. Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study[J]. J Natl Cancer Inst, 2013, 105(8):526-535.
[4] Lambertini M, Santoro L, Del Mastro L, et al. Reproductive behaviors and risk of developing breast cancer according to tumor subtype:a systematic review and meta-analysis of epidemiological studies[J]. Cancer Treat Rev, 2016, 49:65-76.
[5] Rice M S, Eliassen A H, Hankinson S E, et al. Breast cancer research in the nurses' health studies:exposures across the life course[J]. Am J Public Health, 2016, 106(9):1592-1598.
[6] Wang X, Fang L. Advances in circular RNAs and their roles in breast cancer[J]. J Exp Clin Cancer Res, 2018, 37(1):206.
[7] Fan C N, Ma L, Liu N. Systematic analysis of lncRNA-miRNA-mRNA competing endogenous RNA network identifies four-lncRNA signature as a prognostic biomarker for breast cancer[J]. J Transl Med, 2018, 16(1):264.
[8] Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency[J]. Nature, 2013, 495(7441):333-338.
[9] Guo J U, Agarwal V, Guo H, et al. Expanded identification and characterization of mammalian circular RNAs[J]. Genome Biol,2014, 15(7):409.
[10] Salzman J, Gawad C, Wang P L, et al. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types[J]. PLoS One, 2012, 7(2):e30733.
[11] Jeck W R, Sorrentino J A, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats[J]. RNA, 2013, 19(2):141-157.
[12] Tay Y, Rinn J, Pandolfi P P. The multilayered complexity of ceRNA crosstalk and competition[J]. Nature, 2014, 505(7483):344-352.
[13] Hansen T B, Jensen T I, Clausen B H, et al. Natural RNA circles function as efficient microRNA sponges[J]. Nature, 2013, 495(7441):384-388.
[14] Du W W, Yang W, Chen Y, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses[J]. Eur Heart J, 2017, 38(18):1402-1412.
[15] Abdelmohsen K, Panda A C, Munk R, et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by circPABPN1[J]. RNA Biol, 2017, 14(3):361-369.
[16] Bolisetty M T, Graveley B R. Circuitous route to transcription regulation[J]. Mol Cell, 2013, 51(6):705-706.
[17] Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis[J]. Mol Cell, 2017, 66(1):22-37.e29.
[18] Pamudurti N R, Bartok O, Jens M, et al. Translation of CircRNAs[J]. Mol Cell, 2017, 66(1):9-21.e27.
[19] Yin W B, Yan M G, Fang X, et al. Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection[J]. Clin Chim Acta, 2018, 487:363-368.
[20] Lü L, Sun J, Shi P, et al. Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer[J]. 2017, 8(27):44096-44107.
[21] Buenrostro J D, Giresi P G, Zaba L C, et al. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position[J]. Nat Methods, 2013, 10(12):1213-1218.
[22] Corces M R, Trevino A E, Hamilton E G, et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues[J]. Nat Methods, 2017, 14(10):959-962.
[23] Boyle A P, Davis S, Shulha H P, et al. High-resolution mapping and characterization of open chromatin across the genome[J]. Cell, 2008, 132(2):311-322.
[24] Cho S W, Xu J, Sun R, et al. Promoter of lncRNA gene PVT1 is a tumor-suppressor DNA boundary element[J]. Cell, 2018, 173(6):1398-1412.e22.
[25] Maass P G, Glazar P, Memczak S, et al. A map of human circular RNAs in clinically relevant tissues[J]. J Mol Med (Berl), 2017, 95(11):1179-1189.
[26] Ashwal-Fluss R, Meyer M, Pamudurti N R, et al. circRNA biogenesis competes with pre-mRNA splicing[J]. Mol Cell, 2014, 56(1):55-66.
[27] Ivanov A, Memczak S, Wyler E, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals[J]. Cell Rep, 2015, 10(2):170-177.
[28] Shannon P, Markiel A, Ozier O, et al. Cytoscape:a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13(11):2498-2504.
[29] Bindea G, Mlecnik B H, Charoentong P, et al. ClueGO:a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks[J]. 2009, 25(8):1091-1093.
[30] Dong R, Ma X K, Li G W, et al. CIRCpedia v2:an updated database for comprehensive circular RNA annotation and expression comparison[J]. Genomics Proteomics Bioinformatics, 2018, 16(4):226-233.
[31] Shang Q, Yang Z, Jia R, et al. The novel roles of circRNAs in human cancer[J]. Mol Cancer, 2019, 18(1):6.
[32] Li J H, Liu S, Zhou H, et al. starBase v2.0:decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data[J]. Nucleic Acids Res, 2014, 42(Database issue):D92-97.
[33] Zhang X Q, Yang J H. Discovering circRNA-microRNA Interactions from CLIP-Seq Data[J]. Methods Mol Biol, 2018, 1724:193-207.
[34] Xiong D D, Dang Y W, Lin P, et al. A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma[J]. J Transl Med, 2018, 16(1):220.
[35] Zhong X, Tian S, Zhang X, et al. CUE domain-containing protein 2 promotes the warburgeffect and tumorigenesis[J]. EMBO Rep, 2017, 18(5):809-825.
[36] 帅优, 马佩,束永前.环状RNA与肿瘤研究进展[J].中华肿瘤防治杂志,2017,24(4):282-286.
[37] Liu S, Chen L, Xu Y. Significance of PYK2 level as a prognosis predictor in patients with colon adenocarcinoma after surgical resection[J]. Onco Targets Ther, 2018, 11:7625-7634.
[38] Su H, Lin F, Deng X, et al. Profiling and bioinformatics analyses reveal differential circular RNA expression in radioresistant esophageal cancer cells[J]. J Transl Med, 2016, 14(1):225.
[39] Xu J, Liao K, Zhou W. Exosomes regulate the transformation of cancer cells in cancer stem cell homeostasis[J]. Stem Cells Int, 2018, 2018:4837370.
[40] Weiss C N, Ito K. A macro view of microRNAs:the discovery of MicroRNAs and their role in hematopoiesis and hematologic disease[J]. Int Rev Cell Mol Biol, 2017, 334:99-175.
[41] Zeng K, Chen X, Xu M, et al. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7[J]. Cell Death Dis, 2018, 9(4):417.
[42] Wang B G, Li J S, Liu Y F, et al. MicroRNA-200b suppresses the invasion and migration of hepatocellular carcinoma by downregulating RhoA and circRNA_000839[J]. Tumour Biol, 2017, 39(7):1010428317719577.