T Cell Post-Transcriptional miRNA-mRNA Interaction Networks Identify Targets Associated with Susceptibility/Resistance to Collagen-induced Arthritis

Abstract

BackgroundDue to recent studies indicating that the deregulation of microRNAs (miRNAs) in T cells contributes to increased severity of rheumatoid arthritis, we hypothesized that deregulated miRNAs may interact with key mRNA targets controlling the function or differentiation of these cells in this disease.Methodology/Principal FindingsTo test our hypothesis, we used microarrays to survey, for the first time, the expression of all known mouse miRNAs in parallel with genome-wide mRNAs in thymocytes and naïve and activated peripheral CD3+ T cells from two mouse strains the DBA-1/J strain (MHC-H2q), which is susceptible to collagen induced arthritis (CIA), and the DBA-2/J strain (MHC-H2d), which is resistant. Hierarchical clustering of data showed the several T cell miRNAs and mRNAs differentially expressed between the mouse strains in different stages of immunization with collagen. Bayesian statistics using the GenMir++ algorithm allowed reconstruction of post-transcriptional miRNA-mRNA interaction networks for target prediction. We revealed the participation of miR-500, miR-202-3p and miR-30b*, which established interactions with at least one of the following mRNAs: Rorc, Fas, Fasl, Il-10 and Foxo3. Among the interactions that were validated by calculating the minimal free-energy of base pairing between the miRNA and the 3′UTR of the mRNA target and luciferase assay, we highlight the interaction of miR-30b*-Rorc mRNA because the mRNA encodes a protein implicated in pro-inflammatory Th17 cell differentiation (Rorγt). FACS analysis revealed that Rorγt protein levels and Th17 cell counts were comparatively reduced in the DBA-2/J strain.Conclusions/SignificanceThis result showed that the miRNAs and mRNAs identified in this study represent new candidates regulating T cell function and controlling susceptibility and resistance to CIA.

Decreased expression of microRNA‑30b promotes the development of pulpitis by upregulating the expression of interleukin‑6 receptor

“…These five miRNA molecules are encoded by genes located on different chromosomes; however, they have similar seed sequences (33). It has been previously reported that miR-30b may be involved in a number of processes, including inflammatory responses, malignant tumor development and epithelial mesenchymal transition (34)(35)(36)(37), and may have posi- (34)(35)(36)(37), and may have posi-(34-37), and may have positive effects on nerve repair, the inhibition of apoptosis and blood vessel regeneration (34)(35)(36)(37). A previous study has demonstrated that miR-30b is associated with the occurrence and development of human neural tube cells and their tumors; its expression is also associated with schizophrenia (38).…”

Aire Downregulation Is Associated with Changes in the Posttranscriptional Control of Peripheral Tissue Antigens in Medullary Thymic Epithelial Cells

“…This approach was previously described by our group (38, 47, 48). Briefly, double-stranded complementary oligonucleotide pairs containing a portion of the Hmga2 or Prpsap1 3′ UTR with the predicted miRNA binding sites were synthetized by Sigma-Aldrich (St. Louis, MO, USA).…”

Menopause transition promotes distinct modulation of mRNAs and miRNAs expression in calvaria and bone marrow osteoblastic cells

“…The relationship between estrogen deficiency‐induced bone loss and distinct mRNA/miRNA expression profiles has been investigated in the regulation of bone mass, mainly in apendicular bones such as tibia and femur (An et al, ). The knowledge of the functional roles of different genes and their participation in biological processes in conditions like osteoporosis may be achieved through genome research, helping to identify and compare gene expression profile in different environmental conditions (Donate et al, ). Although mRNA is not the final product of a gene, the information on transcript level is necessary to understand the regulatory gene network.…”