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J u l y 2 3 - 2 4 , 2 0 1 8 | R o m e , I t a l y
alliedacademies Joint Event on
Cardiology Congress 2018 & Microbe Infection 2018 Biomedical Research | ISSN: 0976-1683 | Volume 29
2nd World Congress on CARDIOLOGY
MICROBIOLOGY AND MICROBIAL INFECTION
&
39th Annual Congress on
Roopa Biswas et al., Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C1-002
EPIGENETIC REGULATION OF
F508DEL-CFTR CYSTIC FIBROSIS LUNG
DISEASE
Roopa Biswas1, Parameet Kumar1, Raymond A Frizzell2 and
Harvey B Pollard1
1Uniformed Services University of the Health Sciences, USA
2University of Pittsburgh, USA
Cystic fibrosis (CF) is the most common life limiting recessive disease in
the US and is due to mutations in the CFTR gene. CF mutations, of which
the most common is F508del-CFTR, cause a massive pro-inflammatory
phenotype in the lung arising from dysregulated expression of inflammatory
genes. Recently, endogenous non-coding RNA (ncRNA) molecules, including
long non-coding RNAs (LncRNAs) have emerged as important targets in the
frontier of biomedical research. These ncRNAs coordinate with epigenetic
factors to play a crucial role in the regulation of biological processes as
well as in diseases. Long noncoding RNAs (LncRNAs) have emerged as
novel regulators of gene expression, including inflammatory genes. Various
diseases have been associated with the aberrant expression of LncRNAs.
Here we report the role of LncRNA and associated epigenetic factors in
the pathogenesis of CF lung disease. LncRNA nuclear enriched abundant
transcript 1 (NEAT1) is aberrantly upregulated in CF cells including, IB3-
1, CFPAC-1 and CFBE CF cells as well as in lung tissues of CF patients
compared to the respective control cells. NEAT1 has been shown to
regulate the expression of pro-inflammatory cytokine IL-8 in other diseases.
Consistently, we find that suppression of NEAT1 in CF lung epithelial cells
leads to reduced expression of IL-8. Additionally, NEAT1 is induced by p38-
MAPK signaling pathway, which is activated in CF, and our results indicate
that inhibition of this pathway suppresses both NEAT1 as well as IL-8. Our
data indicate that SFPQ, a NEAT1 interacting protein, is down-regulated in
F508del-CFTR CF lung epithelial cells compared to WT- CFTR control cells
and perhaps also contributing to increased expression of IL-8. Consistently,
we find that increased exogenous expression of SFPQ not only attenuates
expression of the pro-inflammatory IL-8 gene, suppresses pro-fibrotic CTGF
protein, but also rescues F508del- CFTR expression in CF lung epithelial cells.
Understanding these mechanisms will lead to novel therapeutic targets for CF
and related pulmonary diseases.
Chronic diseases and even aging itself are known to damage the body
by dys-regulated inflammatory processes. Dysregulated expression of the
pro-inflammatory cytokine and chemokine genes are known to contribute
to chronic inflammatory diseases. Recently, endogenous non-coding RNA
(ncRNA) molecules, including long non-coding RNAs (LncRNAs) and
microRNAs (miRNAs, miRs) have emerged as important targets in the
frontier of biomedical research. These non-coding RNAs have been proven to
be key regulators of gene expression. The ability to detect non-coding RNAs
Roopa Biswas is an Associate Profeesor in Anatomy,
Physiology and Gentics Department in University of
Health Science, USA.
BIOGRAPHY
in biofluids has highlighted their usefulness as
non-invasive markers of diseases, including
lung diseases. The expression of specific non-
coding RNAs is altered in many lung diseases
and their levels in the circulation often reflect
the changes in expression of their lung-
specific counterparts. Therefore, exploiting
these biomolecules as diagnostic tools seems
an obvious goal. Our goal is to investigate the
role of non-coding RNAs in Cystic Fibrosis lung
disease and develop novel anti-inflammatory
therapeutics for pulmonary disorders.