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Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Authors
  • Ahmad, Shama
  • Manzoor, Shajer
  • Siddiqui, Simmone
  • Mariappan, Nithya
  • Zafar, Iram
  • Ahmad, Aamir
  • Ahmad, Aftab
Type
Published Article
Journal
Seminars in Cancer Biology
Publisher
Elsevier
Publication Date
Jan 20, 2021
Identifiers
DOI: 10.1016/j.semcancer.2021.01.003
PMID: 33484868
PMCID: PMC8046427
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

Abstract

Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

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