Abstract
Organ transplantation is the most preferred treatment option for end-stage organ diseases; however, allograft rejection is the major hurdle in successful long-term transplant survival. In spite of developing better HLA matching and more effective immunosuppressive regimen, one-year graft survival has been increased by nearly 90% and the incidence of acute rejection by one-year post-transplantation has been decreased by 12.2% in the last decades, chronic allograft rejection has remained as one of the major obstacles to the long-lasting survival of the transplanted allograft. Therefore, seemingly preventing the allograft rejection and inducing immunological tolerance against transplanted allografts is one of the primary goals in transplantation research to enable long-lasting graft survival. Various mechanisms such as long noncoding RNAs (lncRNAs) have been proposed that induce immune tolerance by modulating the gene expression and regulating innate and adaptive immune responses during transplantation. Besides, because of involvement in regulating epigenetic, transcriptional, and post-translational mechanisms, lncRNAs could affect allograft status. Therefore, these molecules could be considered as the potential targets for prediction, prognosis, diagnosis, and treatment of graft rejection. It is suggested that the noninvasive predictive biomarkers hold promise to overcome the current limitations of conventional tissue biopsy in the diagnosis of rejection. Hence, this review aims to provide a comprehensive overview of lncRNAs and their function to facilitate diagnosis, prognosis, and prediction of the risk of graft rejection, and the suggestive therapeutic choices after transplantation.
Highlights
1.1 Transplantation PerspectiveSolid-organ transplantation is the most preferred treatment option for end-stage organ failure and could ameliorate life expectancy and quality, but allograft rejection is still the main barrier to longterm graft survival
Routine monitoring of transplant recipients includes the measurement of biochemical parameters such as serum creatinine and protein excretion for renal transplant recipients, bilirubin and liver enzymes level consisting of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) for hepatic transplantation, and N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), and cardiac troponin for heart transplant recipients [7, 8]
HOX transcript antisense RNA (HOTAIR), another long non-coding RNAs (lncRNAs), can repress a locus named HoxD by interacting with PRC2; it can interact with a histone demethylase and lead to developing repressive effect on chromatin by removing a histone mark. (II) Modulating DNA methylation; Tcf21 antisense RNA reducing DNA methylation (TARID) is a lncRNA involved in the mechanisms of DNA demethylation. (III) Regulating chromatin remodeling; some lncRNAs play a role in controlling chromatin remodeling complexes which can change nucleosome spacing, such as embryonic ventral forebrain-1 and myosin heavy chain associated RNA transcripts (MHRT) [38]. (IV) Interacting with transcription factors, some lncRNAs take part in signal transduction by regulating initiation, elongation, and termination of transcription factor’s actions [32]
Summary
Solid-organ transplantation is the most preferred treatment option for end-stage organ failure and could ameliorate life expectancy and quality, but allograft rejection is still the main barrier to longterm graft survival. Routine monitoring of transplant recipients includes the measurement of biochemical parameters such as serum creatinine and protein excretion for renal transplant recipients, bilirubin and liver enzymes level consisting of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) for hepatic transplantation, and N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), and cardiac troponin for heart transplant recipients [7, 8] These markers are insensitive and non-specific and only detectable when the allograft dysfunction has occurred. Noncoding RNAs (ncRNAs) are attracting widespread interest due to their ability in affecting the biological pathways which play important roles in health and disease Their stability in tissue and biofluids potentiates them as the appropriate candidates for biomarker discovery. We aimed to conduct a comprehensive literature search and to summarize important results that coming from the original research which have evaluated the lncRNAs and their performance as predictive and/or diagnostic biomarkers for organ transplantation
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