Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

Abstract

Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro study using human renal glomerular endothelial cells (HRGECs) transfected with a miR-650 mimic revealed that key characteristics of acute renal allograft rejection were observed, including apoptosis, the release of cytokines and the chemotaxis of macrophages, while the effects were reduced in HRGECs transfected with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on the 3′-untranslated region of BCL11B mRNA was predicted by computational algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with small interfering RNA (siRNA) significantly increased the apoptotic rate and significantly decreased the proliferation ability of HRGECs compared with the negative control group. HRGECs transfected with a combination of BCL11B siRNA and the miR-650 mimic demonstrated a significant increase in the rate of apoptosis compared with the control. These results suggest that the upregulation of miR-650 contributes to the development of acute renal allograft rejection by suppression of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and BCL11B may represent potential therapeutic targets for the prevention of acute renal allograft rejection.

Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection

“…For example, Liu et al reported that downregulated miR-10b could mediate rejection of renal allografts through inhibiting BCL2L11 expression [ 2 ]. Jin et al decoded a novel mechanism between miR-650 and BCL11B for preventing rejection after kidney transplantation [ 3 ]. Based on the meta-analysis and F344-Lewis rat kidney transplantation model, Liang et al explored the diagnostic role and dynamic change of miR-155 in acute rejection [ 4 ].…”

Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy

“…Numerous genes have been shown to be closely involved in apoptotic and proliferative cellular processes, which is interesting given the established links between apoptosis, vascular calcification and CVD 10 – 12 , 29 , 30 . HIVEP3 31 , EID2 32 , ETS1 33 , MRFAP1 34 , ZNF224 35 , BCL11B 36 , 37 , SKI 38 , 39 , ZMIZ1 40 , GFI1 41 , HDAC4 42 , MAD1L1 43 , NCOR2 44 , 45 , ANKRD11 46 , BANP 47 , and ARID3A 48 , 49 all have functions related to apoptosis, cell survival or cell cycle progression. This highlights the importance of cell cycle activity, apoptosis, and cellular senescence in CKD.…”

Coexpression network analysis of human candida infection reveals key modules and hub genes responsible for host-pathogen interactions

“…Recent advances in microRNA therapeutics have shown the extensive use of microRNAs for cancer and infections ( Rupaimoole and Slack, 2017 ). There has been increased support for microRNA therapeutics in solid organ transplantation, including kidney ( Wilflingseder et al, 2015 ; Jin et al, 2017 ; Ledeganck et al, 2019 ), lung ( Benazzo et al, 2022 ), and heart transplantation ( Hamdorf et al, 2017 ). Candida albicans have been linked to cancerous processes by taking advantage of the compromised immune system ( Ramirez-Garcia et al, 2016 ; Chung et al, 2017 ; Sultan et al, 2022 ).…”