Key result
Secondary analysis of RNA-seq data identified dysregulated lncRNAs in NAFLD patients compared to healthy controls, with LINC01639 regulating apoptosis and cytokine signaling genes.
Why the study?
With NAFLD affecting 25% of the world population, there is an urgent need to understand its disease mechanism, including the role of dysregulated long non-coding RNAs.
Identification of dysregulated lncRNAs in NAFLD and the creation of LiverDB facilitates functional and mechanistic studies of hepatic lncRNAs.
Non-coding RNA signals in NAFLD remain hypothesis-generating; larger studies needed before any clinical role.
The largest solid organ in humans, the liver, performs a variety of functions to sustain life. When damaged, cells in the liver can regenerate themselves to maintain normal liver physiology. However, some damage is beyond repair, which necessitates liver transplantation. Increasing rates of obesity, Western diets (i.e., rich in processed carbohydrates and saturated fats), and cardiometabolic diseases are interlinked to liver diseases, including non-alcoholic fatty liver disease (NAFLD), which is a collective term to describe the excess accumulation of fat in the liver of people who drink little to no alcohol. Alarmingly, the prevalence of NAFLD extends to 25% of the world population, which calls for the urgent need to understand the disease mechanism of NAFLD. Here, we performed secondary analyses of published RNA sequencing (RNA-seq) data of NAFLD patients compared to healthy and obese individuals to identify long non-coding RNAs (lncRNAs) that may underly the disease mechanism of NAFLD. Similar to protein-coding genes, many lncRNAs are dysregulated in NAFLD patients compared to healthy and obese individuals, suggesting that understanding the functions of dysregulated lncRNAs may shed light on the pathology of NAFLD. To demonstrate the functional importance of lncRNAs in the liver, loss-of-function experiments were performed for one NAFLD-related lncRNA, LINC01639, which showed that it is involved in the regulation of genes related to apoptosis, TNF/TGF, cytokine signaling, and growth factors as well as genes upregulated in NAFLD. Since there is no lncRNA database focused on the liver, especially NAFLD, we built a web database, LiverDB, to further facilitate functional and mechanistic studies of hepatic lncRNAs.
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Ilieva et al. (2022) studied Nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease (NAFLD) vs. Healthy and obese individuals was evaluated on Identification of dysregulated long non-coding RNAs (lncRNAs). Secondary analysis of RNA-seq data identified dysregulated lncRNAs in NAFLD patients compared to healthy controls, with LINC01639 regulating apoptosis and cytokine signaling genes.
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