Network analysis of microRNAs, transcription factors, target genes and host genes in human anaplastic astrocytoma

Xue,Luchen; Xu,Zhiwen; Wang,Kunhao; Wang,Ning; Zhang,Xiaoxu; Wang,Shang

doi:10.3892/etm.2016.3272

Network analysis of microRNAs, transcription factors, target genes and host genes in human anaplastic astrocytoma

Authors:
- Luchen Xue
- Zhiwen Xu
- Kunhao Wang
- Ning Wang
- Xiaoxu Zhang
- Shang Wang
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Affiliations: Department of Software Engineering, Jilin University, Changchun, Jilin 130012, P.R. China, Key Laboratory of Symbol Computation and Knowledge Engineering of the Ministry of Education, Jilin University, Changchun, Jilin 130012, P.R. China
Published online on: April 20, 2016 https://doi.org/10.3892/etm.2016.3272
Pages: 437-444

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Abstract

Numerous studies have investigated the roles played by various genes and microRNAs (miRNAs) in neoplasms, including anaplastic astrocytoma (AA). However, the specific regulatory mechanisms involving these genes and miRNAs remain unclear. In the present study, associated biological factors (miRNAs, transcription factors, target genes and host genes) from existing studies of human AA were combined methodically through the interactions between genes and miRNAs, as opposed to studying one or several. Three regulatory networks, including abnormally expressed, related and global networks were constructed with the aim of identifying significant gene and miRNA pathways. Each network is composed of three associations between miRNAs targeted at genes, transcription factors (TFs) regulating miRNAs and miRNAs located on their host genes. Among these, the abnormally expressed network, which involves the pathways of previously identified abnormally expressed genes and miRNAs, partially indicated the regulatory mechanism underlying AA. The network contains numerous abnormal regulation associations when AA emerges. By modifying the abnormally expressed network factors to a normal expression pattern, the faulty regulation may be corrected and tumorigenesis of AA may be prevented. Certain specific pathways are highlighted in AA, for example PTEN which is targeted by miR‑21 and miR‑106b, regulates miR‑25 which in turn targets TP53. PTEN and miR‑21 have been observed to form feedback loops. Furthermore, by comparing and analyzing the pathway predecessors and successors of abnormally expressed genes and miRNAs in three networks, similarities and differences of regulatory pathways may be identified and proposed. In summary, the present study aids in elucidating the occurrence, mechanism, prevention and treatment of AA. These results may aid further investigation into therapeutic approaches for this disease.

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1	Landis SH, Murray T, Bolden S and Wingo PA: Cancer statistics, 1999. CA Cancer J Clin. 49:8–31. 1999. View Article : Google Scholar : PubMed/NCBI
2	Rao SA, Santosh V and Somasundaram K: Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. Mod Pathol. 23:1404–1417. 2010. View Article : Google Scholar : PubMed/NCBI
3	Polishsetty RV, Gautam P, Gupta MK, Sharma R, Uppin MS, Challa S, Ankathi P, Purohit AK, Renu D, Harsha HC, et al: Heterogeneous nuclear ribonucleoproteins and their interactors are a major class of deregulated proteins in anaplastic astrocytoma: A grade III malignant glioma. J Proteome Res. 12:3128–3138. 2013. View Article : Google Scholar : PubMed/NCBI
4	Tanwar MK, Glibert MR and Holland EC: Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res. 62:4364–4368. 2002.PubMed/NCBI
5	Ugur HC, Taspinar M, Ilgaz S, Sert F, Canpinar H, Rey JA, Castresana JS and Sunguroglu A: Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide-lomeguatrib combination. Mol Biol Rep. 41:697–703. 2014. View Article : Google Scholar : PubMed/NCBI
6	Tran DH, Satou K, Ho TB and Pham TH: Computational discovery of miR TF regulatory modules in human genome. Bioinformation. 4:371–377. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hobert O: Gene regulation by transcription factors and microRNAs. Science. 319:W1785–W1786. 2008. View Article : Google Scholar
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Zhi F, Zhou G, Shao N, Xia X, Shi Y, Wang Q, Zhang Y, Wang R, Xue L, Wang S, et al: MiR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK. PLoS One. 8:e723902013. View Article : Google Scholar : PubMed/NCBI
10	Rodriguez A, Griffiths-Jones S, Ashurst JL and Bradley A: Identification of mammalian microRNA host genes and transcription units. Genome Res. 14:1902–1910. 2004. View Article : Google Scholar : PubMed/NCBI
11	Baskerville S and Bartel DP: Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 11:241–247. 2005. View Article : Google Scholar : PubMed/NCBI
12	Cao G, Huang B, Liu Z, Zhang J, Xu H, Xia W, Li J, Li S, Chen L, Ding H, et al: Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochem Biophys Res Commun. 396:978–982. 2010. View Article : Google Scholar : PubMed/NCBI
13	Sandro PC, Jose DA, Carlos AC, Cristovam SN, Stela VP, Sonia MM, Marcelo JDS and Euclides TDR: Evaluation of the microvascular density in astrocytomas in adults correlated using SPECT-MIBI. Exp Ther Med. 1:293–299. 2010.
14	Wang K, Xu Z, Wang N, Xu T and Zhu M: MicroRNA and gene networks in human diffuse large B-cell lymphoma. Oncol Lett. 8:2225–2232. 2014.PubMed/NCBI
15	Zhu MH, Xu ZW, Wang KH, Wang N, Zhu MY and Wang S: MicroRNA and gene networks in human Hodgkin's lymphoma. Mol Med Rep. 8:1747–1754. 2013.PubMed/NCBI
16	Killela PJ, Pirozzi CJ, Reitman ZJ, Jones S, Rasheed BA, Lipp E, Friedman H, Friedman AH, He Y, McLendon RE, et al: The genetic landscape of anaplastic astrocytoma. Oncotarget. 5:1452–1457. 2014. View Article : Google Scholar : PubMed/NCBI
17	Guan YL, Mizoguchi M, Yoshimoto K, Hata N, Shono T, Suzuki SO, Araki Y, Kuga D, Nakamizo A, Amano T, et al: MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance. Clin Cancer Res. 16:4289–4297. 2010. View Article : Google Scholar : PubMed/NCBI
18	Li J, Xu ZW, Wang KH, Wang N, Li DQ and Wang S: Networks of microRNAs and genes in retinoblastomas. Asian Pac J Cancer Prev. 14:6631–6636. 2013. View Article : Google Scholar
19	Chekmenev DS, Haid C and Kel AE: P-Match: Transcription factor binding site search by combining patterns and weight matrices. Nucleic Acids Res. 33:W432–W437. 2005. View Article : Google Scholar : PubMed/NCBI
20	Papadopoulos GL, Reczko M, Simossis VA, Sethupathy P and Hatzigeorgiou AG: The database of experimentally supported targets: A functional update of TarBase. Nucleic Acids Res. 37:D155–D158. 2009. View Article : Google Scholar : PubMed/NCBI
21	Hsu SD, Tseng YT, Shrestha S, Lin YL, Khaleel A, Chou CH, Chu CF, Huang HY, Lin CM, Ho SY, et al: miRTarBase update 2014: An information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 42:D78–D85. 2014. View Article : Google Scholar : PubMed/NCBI
22	Xiao F, Zuo Z, Cai G, Kang S, Gao X and Li T: miRecords: An integrated resource for microRNA-target interactions. Nucleic Acids Res. 37:D105–D110. 2009. View Article : Google Scholar : PubMed/NCBI
23	Wang J, Lu M, Qiu CX and Cui QH: TransmiR: A transcription factor-microRNA regulation database. Nucleic Acids Res. 38:D119–D122. 2010. View Article : Google Scholar : PubMed/NCBI
24	Kozomara A and Griffiths-Jones S: miRBase: Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39:D152–D157. 2011. View Article : Google Scholar : PubMed/NCBI
25	Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M, Nativ N, Bahir I, Doniger T, Krug H, et al: GeneCards Version 3: The human gene integrator. Database (Oxford). 2010:baq0202010. View Article : Google Scholar : PubMed/NCBI
26	Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, et al: The UCSC genome browser database: Update 2011. Nucleic Acids Res. 39:D876–D882. 2011. View Article : Google Scholar : PubMed/NCBI
27	Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O'Fallon JR, Schaefer PL, Scheithauer BW, James CD, et al: PTEN mutation, EGFR amplification and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst. 93:1246–1256. 2001. View Article : Google Scholar : PubMed/NCBI
28	Chang CL: Genome-wide oligonucleotide microarray analysis of gene-expression profiles of Taiwanese patients with anaplastic astrocytoma and glioblastoma multiforme. J Biomol Screen. 13:912–921. 2008. View Article : Google Scholar : PubMed/NCBI
29	Shu M, Zheng X, Wu S, Lu H, Leng T, Zhu W, Zhou Y, Ou Y, Lin X, Lin Y, et al: Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells. Mol Cancer. 10:592011. View Article : Google Scholar : PubMed/NCBI
30	Anselmo NP, Rey JA, Almeida LO, Custodio AC, Almeida JR, Clara CA, Santos MJ and Casartelli C: Concurrent sequence variation of TP53 and TP73 genes in anaplastic astrocytoma. Genet Mol Res. 8:1257–1263. 2009. View Article : Google Scholar : PubMed/NCBI
31	Ushio Y, Tada K, Shiraishi S, Kamiryo T, Shinojima N, Kochi M and Saya H: Correlation of molecular genetic analysis of p53, MDM2, P16, PTEN and EGFR and survival of patients with anaplastic astrocytoma and glioblastoma. Front Biosci. 8:e281–e288. 2003. View Article : Google Scholar : PubMed/NCBI
32	Zhi F, Chen X, Wang SN, Xia X, Shi Y, Guan W, Shao N, Qu H, Yang C, Zhang Y, et al: The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma. Eur J Cancer. 46:1640–1649. 2010. View Article : Google Scholar : PubMed/NCBI