RESUMO
The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.
RESUMO
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.
