A Compelling Look At Long Non-Coding RNA MALAT1's Role In Lung Diseases, Including COVID-19

Medical News: An intriguing discovery at the intersection of genetics and medical research has been gaining significant attention in recent years. Long non-coding RNAs (lncRNAs) i.e. RNA molecules exceeding 200 nucleotides in length, which lack the ability to code for proteins, have emerged as a fascinating subject of study.


 
Notably, one lncRNA, known as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), has attracted the attention of researchers from prestigious institutions such as Shengjing Hospital of China Medical University and Stanford University. Existing data suggest that MALAT1 plays a crucial role in the pathogenesis of various lung diseases, including asthma, chronic obstructive pulmonary diseases (COPD), COVID-19, acute respiratory distress syndrome (ARDS), lung cancers, and pulmonary hypertension.
 
Understanding the Enigma of lncRNAs
According to the GENCODE consortium, nearly 20,000 lncRNAs have been identified in humans. These lncRNAs interact with mRNA, miRNA, DNA, and proteins, influencing gene expression at numerous cellular and molecular levels. They've emerged as key players in diverse biological processes, from cell proliferation and apoptosis to angiogenesis, migration, and metabolism.
 
In the world of genetics, lncRNAs have gained considerable attention due to their role in various diseases. Among these, MALAT1 stands out for its association with numerous diseases, including cancers and cardiovascular diseases. Recent studies have suggested that aberrant expression of MALAT1 is significantly involved in the pathogenesis of various lung diseases, including COVID-19.
 
Unraveling MALAT1’s Role in Lung Diseases
Lung diseases, including asthma, COPD, lung cancer, and COVID-19, are among the leading causes of death worldwide. Identifying novel therapeutic interventions is an urgent priority, and understanding the molecular mechanisms of diseases is crucial.
 
MALAT1, located in human chromosome 11q13.1, is a nuclear-enriched and highly conserved lncRNA. It regulates pre-mRNA splicing, transcription, and post-transcriptional modifications. Moreover, it can act as a competing endogenous RNA or miRNA sponge, regulating gene expression. An abundance of evidence suggests that MALAT1 has significant therapeutic and prognostic implications in various cancers.
 
In the context of lung diseases, recent studies and Medical News coverages show MALAT1's potential as a therapeutic target and biomarker. For instance, research has linked MALAT1 to asthma's pathogenesis and progression, with asthma patients exhibiting elevated levels of MALAT1.
 
Similarly, in idiopathic pulmonary fibrosis (IPF), a progressive lung disease with high mortality rates, MALAT1 has emerged as a major regulator.
 
Furthermore, MALAT1 overexpression has been observed in ARDS patients, indicating a potential role in the disease's pathogenesis. In patients with COPD, a chronic inflammatory lung condition, MALAT1 levels have been consistently elevated, correlating with disease severity and inflammatory cytokines. In pulmonary arterial hypertension (PAH), a life-threatening conditi on characterized by high blood pressure in the lungs' arteries, MALAT1 has been identified as a potential player in disease development.
 
The numerous pieces of evidence amassed over recent years strongly imply that MALAT1 is a critical player in the development and progression of various lung diseases. The involvement of MALAT1 in the pathogenesis of these diseases often revolves around its ability to regulate the proliferation, migration, and survival of cells in the lung tissue.
 
Targeting MALAT1: A Therapeutic Promise
Given the crucial role of MALAT1 in lung diseases, it's an attractive target for therapeutic interventions. For example, studies have shown that knockdown of MALAT1 can reverse inflammation and mitigate bronchial and tracheal smooth muscle cell injury in asthma, suggesting the potential for MALAT1-targeted therapies in lung diseases. Moreover, several drugs have demonstrated potential for improving tissue injury by targeting MALAT1.
 
The potential utility of MALAT1 as a therapeutic target for lung diseases is further underscored by the fact that it can be effectively targeted by various strategies. One such strategy involves the use of RNA interference (RNAi), a potent and versatile tool for silencing gene expression. RNAi-based approaches can be used to specifically silence MALAT1 expression, thereby modulating its disease-causing effects. Moreover, advances in drug discovery have led to the identification of several drugs that can target MALAT1, providing further avenues for therapeutic intervention.
 
MALAT1 And COVID-19
An intriguing aspect of MALAT1’s role in lung diseases is its association with COVID-19. The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has wreaked havoc across the globe, posing unprecedented challenges to global health. A significant fraction of patients with COVID-19 develop severe lung disease, including pneumonia and ARDS, which often results in death. Given the critical role of MALAT1 in lung disease pathogenesis, researchers have speculated that it may also be involved in the lung complications associated with COVID-19. Although more research is needed to ascertain this link, the potential of MALAT1 as a therapeutic target for COVID-19-associated lung disease is certainly an exciting prospect.
 
MALAT1 As A Biomarker
In addition to its potential as a therapeutic target, MALAT1 also holds promise as a diagnostic and prognostic biomarker for lung diseases. The level of MALAT1 expression in body fluids, such as blood and bronchoalveolar lavage fluid, can serve as an indicator of disease presence and severity. Moreover, changes in MALAT1 expression levels could also provide clues about the patient’s response to therapy, making it a valuable tool for disease monitoring.
 
Conclusion
Despite the significant strides made in understanding the role of MALAT1 in lung diseases, several questions remain unanswered. For instance, the precise molecular mechanisms through which MALAT1 contributes to disease pathogenesis are still not entirely clear. Moreover, while we know that MALAT1 interacts with various other biomolecules, such as miRNAs and proteins, to exert its effects, the full spectrum of these interactions is yet to be elucidated.

Future research should focus on addressing these gaps in our knowledge. Further elucidation of the molecular mechanisms involving MALAT1 could pave the way for the development of more effective therapeutic strategies. Moreover, the identification of additional MALAT1-interacting molecules could provide new targets for drug development. Lastly, more work is needed to validate MALAT1 as a biomarker for lung diseases and to determine its utility in different patient populations and disease stages.
 
MALAT1 is an exciting molecule that holds immense potential for the diagnosis, prognosis, and treatment of lung diseases.
 
The study review was published in the peer reviewed journal: Frontiers In Cell and Developmental Biology.
https://www.frontiersin.org/articles/10.3389/fcell.2023.1149499/full
 
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