Open Access

Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis

  • Authors:
    • Chau‑Chyun Sheu
    • Wei‑An Chang
    • Ming‑Ju Tsai
    • Ssu‑Hui Liao
    • Inn‑Wen Chong
    • Po‑Lin Kuo
  • View Affiliations

  • Published online on: January 31, 2019     https://doi.org/10.3892/ijmm.2019.4086
  • Pages: 1643-1656
  • Copyright: © Sheu 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 a lethal fibrotic lung disease with an increasing global burden. It is hypothesized that fibroblasts have a number of functions that may affect the development and progression of IPF. However, the present understanding of cellular and molecular mechanisms associated with fibroblasts in IPF remains limited. The present study aimed to identify the dysregulated genes in IPF fibroblasts, elucidate their functions and explore potential microRNA (miRNA)‑mRNA interactions. mRNA and miRNA expression profiles were obtained from IPF fibroblasts and normal lung fibroblasts using a next‑generation sequencing platform, and bioinformatic analyses were performed in a step‑wise manner. A total of 42 dysregulated genes (>2 fold‑change of expression) were identified, of which 5 were verified in the Gene Expression Omnibus (GEO) database analysis, including the upregulation of neurotrimin (NTM), paired box 8 (PAX8) and mesoderm development LRP chaperone, and the downregulation of ITPR interacting domain containing 2 and Inka box actin regulator 2 (INKA2). Previous data indicated that PAX8 and INKA2 serve roles in cell growth, proliferation and survival. Gene Ontology analysis indicated that the most significant function of these 42 dysregulated genes was associated with the composition and function of the extracellular matrix (ECM). A total of 60 dysregulated miRNAs were also identified, and 1,908 targets were predicted by the miRmap database. The integrated analysis of mRNA and miRNA expression data, combined with GEO verification, finally identified Homo sapiens (hsa)‑miR‑1254‑INKA2 and hsa‑miR‑766‑3p‑INKA2 as the potential miRNA‑mRNA interactions in IPF fibroblasts. In summary, the results of the present study suggest that dysregulation of PAX8, hsa‑miR‑1254‑INKA2 and hsa‑miR‑766‑3p‑INKA2 may promote the proliferation and survival of IPF fibroblasts. In the functional analysis of the dysregulated genes, a marked association between fibroblasts and the ECM was identified. These data improve the current understanding of fibroblasts as key cells in the pathogenesis of IPF. As a screening study using bioinformatics approaches, the results of the present study require additional validation.
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April-2019
Volume 43 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Sheu CC, Chang WA, Tsai MJ, Liao SH, Chong IW and Kuo PL: Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis. Int J Mol Med 43: 1643-1656, 2019.
APA
Sheu, C., Chang, W., Tsai, M., Liao, S., Chong, I., & Kuo, P. (2019). Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis. International Journal of Molecular Medicine, 43, 1643-1656. https://doi.org/10.3892/ijmm.2019.4086
MLA
Sheu, C., Chang, W., Tsai, M., Liao, S., Chong, I., Kuo, P."Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis". International Journal of Molecular Medicine 43.4 (2019): 1643-1656.
Chicago
Sheu, C., Chang, W., Tsai, M., Liao, S., Chong, I., Kuo, P."Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis". International Journal of Molecular Medicine 43, no. 4 (2019): 1643-1656. https://doi.org/10.3892/ijmm.2019.4086