EpisomiR, a New Family of miRNAs, and Its Possible Roles in Human Diseases

Abstract

MicroRNAs (miRNAs) are synthesized through a canonical pathway and play a role in human diseases, such as cancers and cardiovascular, neurodegenerative, psychiatric, and chronic inflammatory diseases. The development of sequencing technologies has enabled the identification of variations in noncoding miRNAs. These miRNA variants, called isomiRs, are generated through a non-canonical pathway, by several enzymes that alter the length and sequence of miRNAs. The isomiR family is, now, expanding further to include episomiRs, which are miRNAs with different modifications. Since recent findings have shown that isomiRs reflect the cell-specific biological function of miRNAs, knowledge about episomiRs and isomiRs can, possibly, contribute to the optimization of diagnosis and therapeutic technology for precision medicine.

Updated immunomodulatory roles of gut flora and microRNAs in inflammatory bowel diseases

“…Excessive inflammation is a hallmark of inflamed colon tissue and blood in IBD hosts, and can be regulated by miRNAs in a direct or indirect way. As a whole, miRNAs can alter the production of local and/or systemic pro/anti-inflammatory factors to exasperate or improve IBD [ 65 – 68 ]. Since they have specific differential expressions in peripheral blood and colon tissues, a plenty of miRNAs are usually employed to differentiate UC and CD in clinical diagnosis [ 69 ].…”

“…An autophagy process requires synergistic action of a variety of proteins, such as NOD2, IRGM, vimentin and multiprotein complexes (ATG16L1 and ATG5-ATG12) [ 78 ]. Many miRNAs can regulate these proteins, thereby controlling intestinal mucosal immunity and epithelial functions [ 68 , 79 , 80 ]. During the endoplasmic reticulum stress response, a group of miRNAs can utilize autophagy to regulate the unfolded protein response (UPR), a process that contributes to intestinal fibrosis in IBD [ 81 ].…”

“…Incremental documents uncover the implications of innate and adaptive immune cells, including epithelial cells [ 71 – 77 , 79 , 80 , 91 – 93 ], macrophage [ 68 , 86 , 94 – 109 ], neutrophil [ 110 – 113 ], NK cells [ 114 ], DCs [ 67 , 115 – 122 ], Th17 cells [ 65 , 123 – 129 ], Tregs [ 66 , 130 , 131 ] in IBD amelioration and exacerbation upon altered miRNA profiling (Table 2 ).…”

Pancreatic Cancer Research beyond DNA Mutations

“…Thus, SAM-dependent RNA methylation is a good candidate for biomarkers in liquid biopsy [ 91 ]. Analysis through another method, i.e., current tunnel sequencing, revealed cancer-specific methylation of miRNAs [ 92 ], suggesting that the epitranscriptomic modification of miRNAs, named eisomiRs, can provide the potential for biomarkers [ 93 ]. In PDAC, the methylation of adenosine of polo-like kinase 1 ( PLK1 ) plays a role in regulating cell cycle homeostasis as a potential target of radiotherapy in PDAC [ 94 ].…”

State-of-the-Art Cancer Biology, Biodiagnostics and Therapeutics in Japan

“…A service for risk testing pancreatic cancer is now also available in the market [1]. The two studies by Arao et al and Tanaka et al discuss molecular mechanisms of miRNA and a ubiquitously expressed gene Mint3, both of which are promising candidates for detecting and treating cancers and other diseases [2,3]. Existing miRNA variants with different modifications in terms of sequence substitutions, differences in length, and chemical modifications on specific nucleotides are found in the body fluid depending on whether the ailment relates to cancer, cardiovascular, neurodegenerative, or psychiatric disorders, or chronic inflammation.…”