Molecular pathogenesis involved in human idiopathic pulmonary fibrosis based on an integrated microRNA‑mRNA interaction network

Wang,Lijing; Huang,Wei; Zhang,Lemeng; Chen,Qiong; Zhao,Hongjun

doi:10.3892/mmr.2018.9456

Molecular pathogenesis involved in human idiopathic pulmonary fibrosis based on an integrated microRNA‑mRNA interaction network

Authors:
- Lijing Wang
- Wei Huang
- Lemeng Zhang
- Qiong Chen
- Hongjun Zhao
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Affiliations: Department of Gerontology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Division of Cellular Therapy, Duke University, Durham, NC 27710, USA, Department of Thoracic Oncology, Hunan Cancer Hospital, Changsha, Hunan 410008, P.R. China, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: September 5, 2018 https://doi.org/10.3892/mmr.2018.9456
Pages: 4365-4373
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Idiopathic pulmonary fibrosis (IPF) is considered to be an ailment of the lungs that cannot be cured, wherein the lung tissues are characterized by increased thickness and stiffness, and/or scars. Despite the fact that extensive success has been achieved regarding the molecular diagnostics and pathobiology, the basic pathogenesis associated with IPF has not yet been fully elucidated and requires further clarification. In the current research, the changes in microRNA (miRNA) and mRNA expression in IPF were investigated through an integrative network technique. The authentic miRNA and mRNA expression profiling datasets were downloaded from Gene Expression Omnibus, followed by identification of differentially expressed miRNAs and mRNAs with use of the Significance Analysis of Microarrays algorithm. Expansion of the molecular targets associated with miRNAs was performed with the use of CyTargetLinker in Cytoscape, which was succeeded by validation with the use of mRNA array expression profiling. The incorporated miRNA‑mRNA network covered 27 genes, in addition to 22 miRNAs that were associated with IPF development. As revealed by the functional enrichment analysis, the cytokine‑cytokine receptor interaction and glycine, serine and threonine metabolism signalling pathways were extensively associated with IPF development. Overall, the present incorporated network illustrated the key link between miRNA and genes in IPF; in particular, it was elucidated that miR‑409‑5p and has‑miR‑376c, together with their target genes (C‑C motif chemokine ligand 20 and oncostatin M), are likely candidates involved in the promotion of IPF initiation and progression.

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1	Meltzer EB and Noble PW: Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 3:82008. View Article : Google Scholar : PubMed/NCBI
2	Cai M, Zhu M, Ban C, Su J, Ye Q, Liu Y, Zhao W, Wang C and Dai H: Clinical features and outcomes of 210 patients with idiopathic pulmonary fibrosis. Chin Med J (Engl). 127:1868–1873. 2014.PubMed/NCBI
3	Ley B, Collard HR and King TE Jr: Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 183:431–440. 2011. View Article : Google Scholar : PubMed/NCBI
4	King TE Jr, Pardo A and Selman M: Idiopathic pulmonary fibrosis. Lancet. 378:1949–1961. 2011. View Article : Google Scholar : PubMed/NCBI
5	Rajasekaran S, Rajaguru P and Sudhakar Gandhi PS: MicroRNAs as potential targets for progressive pulmonary fibrosis. Front Pharmacol. 6:2542015. View Article : Google Scholar : PubMed/NCBI
6	Zhu W and Chen YP: Computational developments in microRNA-regulated protein-protein interactions. BMC Syst Biol. 8:142014. View Article : Google Scholar : PubMed/NCBI
7	Meltzer EB, Barry WT, D'Amico TA, Davis RD, Lin SS, Onaitis MW, Morrison LD, Sporn TA, Steele MP and Noble PW: Bayesian probit regression model for the diagnosis of pulmonary fibrosis: Proof-of-principle. BMC Med Genomics. 4:702011. View Article : Google Scholar : PubMed/NCBI
8	Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, et al: Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol. 47:879–887. 2012. View Article : Google Scholar : PubMed/NCBI
9	Qiu X, Wu H and Hu R: The impact of quantile and rank normalization procedures on the testing power of gene differential expression analysis. BMC Bioinformatics. 14:1242013. View Article : Google Scholar : PubMed/NCBI
10	Fan S, Pan Z, Geng Q and Li X, Wang Y, An Y, Xu Y, Tie L, Pan Y and Li X: Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles. PLoS One. 8:e671422013. View Article : Google Scholar : PubMed/NCBI
11	Fan S and Li X, Tie L, Pan Y and Li X: KIAA0101 is associated with human renal cell carcinoma proliferation and migration induced by erythropoietin. Oncotarget. 7:13520–13537. 2016.PubMed/NCBI
12	Fan S, Geng Q, Pan Z and Li X, Tie L, Pan Y and Li X: Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 6:1522012. View Article : Google Scholar : PubMed/NCBI
13	Kutmon M, Kelder T, Mandaviya P, Evelo CT and Coort SL: CyTargetLinker: A cytoscape app to integrate regulatory interactions in network analysis. PLoS One. 8:e821602013. View Article : Google Scholar : PubMed/NCBI
14	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
15	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 : PubMed/NCBI
16	Maimaiti A, Abudoukeremu K, Tie L, Pan Y and Li X: MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia. Gene. 558:271–277. 2015. View Article : Google Scholar : PubMed/NCBI
17	Li Y, Xu J, Chen H, Bai J, Li S, Zhao Z, Shao T, Jiang T, Ren H, Kang C and Li X: Comprehensive analysis of the functional microRNA-mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression. Nucleic Acids Res. 41:e2032013. View Article : Google Scholar : PubMed/NCBI
18	Dong L, Bi KH, Huang N and Chen CY: Biological analysis of chronic lymphocytic leukemia: Integration of mRNA and microRNA expression profiles. Genet Mol Res. 15:2016. View Article : Google Scholar :
19	Zhu J, Wang S, Zhang W, Qiu J, Shan Y, Yang D and Shen B: Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network. Oncotarget. 6:43819–43830. 2015. View Article : Google Scholar : PubMed/NCBI
20	Li J, Fan S, Han D, Xie J, Kuang H and Ge P: Microarray gene expression profiling and bioinformatics analysis of premature ovarian failure in a rat model. Exp Mol Pathol. 97:535–541. 2014. View Article : Google Scholar : PubMed/NCBI
21	Liu PF, Jiang WH, Han YT, He LF, Zhang HL and Ren H: Integrated microRNA-mRNA analysis of pancreatic ductal adenocarcinoma. Genet Mol Res. 14:10288–10297. 2015. View Article : Google Scholar : PubMed/NCBI
22	Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, et al: Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 182:220–229. 2010. View Article : Google Scholar : PubMed/NCBI
23	Pandit KV, Milosevic J and Kaminski N: MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. 157:191–199. 2011. View Article : Google Scholar : PubMed/NCBI
24	Yang S, Banerjee S, de Freitas A, Sanders YY, Ding Q, Matalon S, Thannickal VJ, Abraham E and Liu G: Participation of miR-200 in pulmonary fibrosis. Am J Pathol. 180:484–493. 2012. View Article : Google Scholar : PubMed/NCBI
25	Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV and Lü J: miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol. 45:287–294. 2011. View Article : Google Scholar : PubMed/NCBI
26	Wang Y, Huang C, Reddy Chintagari N, Bhaskaran M, Weng T, Guo Y, Xiao X and Liu L: miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/β-catenin pathway. Nucleic Acids Res. 41:3833–3844. 2013. View Article : Google Scholar : PubMed/NCBI
27	Yang S, Cui H, Xie N, Icyuz M, Banerjee S, Antony VB, Abraham E, Thannickal VJ and Liu G: miR-145 regulates myofibroblast differentiation and lung fibrosis. FASEB J. 27:2382–2391. 2013. View Article : Google Scholar : PubMed/NCBI
28	Nho RS, Im J, Ho YY and Hergert P: MicroRNA-96 inhibits FoxO3a function in IPF fibroblasts on type I collagen matrix. Am J Physiol Lung Cell Mol Physiol. 307:L632–L642. 2014. View Article : Google Scholar : PubMed/NCBI
29	Liang H, Xu C, Pan Z, Zhang Y, Xu Z, Chen Y, Li T, Li X, Liu Y, Huangfu L, et al: The antifibrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fibrosis. Mol Ther. 22:1122–1133. 2014. View Article : Google Scholar : PubMed/NCBI
30	Dakhlallah D, Batte K, Wang Y, Cantemir-Stone CZ, Yan P, Nuovo G, Mikhail A, Hitchcock CL, Wright VP, Nana-Sinkam SP, et al: Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med. 187:397–405. 2013. View Article : Google Scholar : PubMed/NCBI
31	Yang G, Yang L, Wang W, Wang J, Wang J and Xu Z: Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fibrosis disease progression. Gene. 562:138–144. 2015. View Article : Google Scholar : PubMed/NCBI
32	Frick VO, Rubie C, Keilholz U and Ghadjar P: Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview. World J Gastroenterol. 22:833–841. 2016. View Article : Google Scholar : PubMed/NCBI
33	Cheluvappa R: Experimental appendicitis and appendectomy modulate the CCL20-CCR6 axis to limit inflammatory colitis pathology. Int J Colorectal Dis. 29:1181–1188. 2014. View Article : Google Scholar : PubMed/NCBI
34	Marchal-Sommé J, Uzunhan Y, Marchand-Adam S, Kambouchner M, Valeyre D, Crestani B and Soler P: Dendritic cells accumulate in human fibrotic interstitial lung disease. Am J Respir Crit Care Med. 176:1007–1014. 2007. View Article : Google Scholar : PubMed/NCBI
35	O'Hara KA, Kedda MA, Thompson PJ and Knight DA: Oncostatin M: An interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma. Clin Exp Allergy. 33:1026–1032. 2003. View Article : Google Scholar : PubMed/NCBI
36	Mozaffarian A, Brewer AW, Trueblood ES, Luzina IG, Todd NW, Atamas SP and Arnett HA: Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis. J Immunol. 181:7243–7253. 2008. View Article : Google Scholar : PubMed/NCBI
37	Josson S, Gururajan M, Hu P, Shao C, Chu GY, Zhau HE, Liu C, Lao K, Lu CL, Lu YT, et al: miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer. Clin Cancer Res. 20:4636–4646. 2014. View Article : Google Scholar : PubMed/NCBI