Long Non-Coding RNAs and Their “Discrete” Contribution to IBD and Johne’s Disease—What Stands out in the Current Picture? A Comprehensive Review

Abstract

Non-coding RNAs (ncRNA) have paved the way to new perspectives on the regulation of gene expression, not only in biology and medicine, but also in associated fields and technologies, ensuring advances in diagnostic means and therapeutic modalities. Critical in this multistep approach are the associations of long non-coding RNA (lncRNA) with diseases and their causal genes in their networks of interactions, gene enrichment and expression analysis, associated pathways, the monitoring of the involved genes and their functional roles during disease progression from one stage to another. Studies have shown that Johne’s Disease (JD), caused by Mycobacterium avium subspecies partuberculosis (MAP), shares common lncRNAs, clinical findings, and other molecular entities with Crohn’s Disease (CD). This has been a subject of vigorous investigation owing to the zoonotic nature of this condition, although results are still inconclusive. In this review, on one hand, the current knowledge of lncRNAs in cells is presented, focusing on the pathogenesis of gastrointestinal-related pathologies and MAP-related infections and, on the other hand, we attempt to dissect the associated genes and pathways involved. Furthermore, the recently characterized and novel lncRNAs share common pathologies with IBD and JD, including the expression, molecular networks, and dataset analysis results. These are also presented in an attempt to identify potential biomarkers pertinent to cattle and human disease phenotypes.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

“…Notably, a lncRNA ENSG00000254645 , stands out as it ranks among the top ten downregulated genes in the IBD vs. Control comparison. This transcript has previously been associated with IBD ( 33 ). In our analysis, this transcript demonstrates significant downregulation in both the CD vs. Control and UC vs. Control comparisons ( Supplementary Figure 3 ).…”

“…One notable discovery is a novel transcript, ENSG00000254645, which is downregulated in IBD patients compared to non-IBD subjects. Recently, this transcript was reported to be down regulated in CD (33). This transcript is a long non-coding RNA (lncRNA) located on chromosome 11, with the SOX6 (SRY-Box Transcription Factor 6) gene upstream and INSC (Inscuteable Spindle Orientation Adaptor) and the calcitonin genes (CALCa and CALCB) downstream (55)(56)(57).…”

MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

“…The RNA that is not translated to protein is called non-coding RNA (ncRNA) and includes long-non coding RNAs (lncRNAs) and microRNAs (miRNAs), among others. LncRNAs are now emerging as important regulators of innate and adaptive immune responses, and there is growing evidence that lncRNAs contribute to the pathogenesis of human diseases like Crohn’s disease and inflammatory bowel disease 22 – 25 . MiRNAs are highly conserved small ncRNAs (18 to 25 nucleotides long) that regulate mRNA expression by binding to the 3’-untranslated region of their target mRNAs 26 .…”

The Effect of Melatonin on the Expression of H19, MALAT, HOTAIR, THRIL, and NOS Activity in Leishmania major-Infected Macrophages

“…H19, metastasis-associated lung adenocarcinoma transcript 1 (MALAT), HOX antisense intergenic RNA (HOTAIR), and TNF and HNRNPL Related Immunoregulatory Long Non-Coding RNA (THRIL) are lncRNAs that regulate gene expression in macrophages. They are instrumental in the differentiation, polarization, and activation of macrophages, as well as in the regulation of inflammatory responses (16,17). Therefore, influencing these lncRNAs may enhance immune responses to infections.…”