Small RNA profiles of HTLV‑1 asymptomatic carriers with monoclonal and polyclonal rearrangement of the T‑cell antigen receptor γ‑chain using massively parallel sequencing: A pilot study

Abstract

In the present pilot study, massively parallel sequencing (MPS) technology was used to investigate cellular small RNA (sRNA) levels in the peripheral blood mononuclear cells (PBMCs) of human T-lymphotropic virus type I (HTLV-I) infected asymptomatic carriers with monoclonal (ASM) and polyclonal (ASP) T cell receptor (TCR) γ gene. Blood samples from 15 HTLV-I asymptomatic carriers (seven ASM and eight ASP) were tested for the clonal TCR-γ gene and submitted for sRNA library construction together with blood samples of five healthy controls (HCs) using Illumina sequencing platform. The sRNA-sequencing reads were aligned, annotated and profiled using various bioinformatics tools. Based on these results, possible markers were validated in the study samples by performing reverse transcription-quantitative (RT-q)PCR analysis. A total of 76 known sRNAs and 52 putative novel sRNAs were identified. Among them, 44 known and 34 potential novel sRNAs were differentially expressed in the ASM and ASP libraries compared with HCs. In addition, 10 known sRNAs were exclusively dysregulated in the ASM group and one (transfer RNA 65) was significantly upregulated in the ASP group. Homo sapiens (hsa) microRNA (miRNA/mir)-23a-3p,-28-5p, hsa-let-7e-5p and hsa-mir-28-3p and-361-5p were the most abundantly upregulated mature miRNAs and hsa-mir-363-3p,-532-5p,-106a-5p,-25-3p and-30e-5p were significantly downregulated miRNAs (P<0.05) with a >2-fold difference between the ASM and ASP groups compared with HCs. Based on these results, hsa-mir-23a-3p and-363-3p were selected for additional validation. However, the quantification of these two miRNAs using RT-qPCR did not provide any significant differences. While the present study failed to identify predictive sRNA markers to distinguish between ASM and ASP, the MPS results revealed differential sRNA expression profiles in the PBMCs of HTLV-1 asymptomatic carriers (ASM and ASP) compared with HCs.

Characterization of microRNA expression in B cells derived from Japanese black cattle naturally infected with bovine leukemia virus by deep sequencing

“…Moreover, 12 of the 15 bta-miRNAs with relatively weaker negative correlations to AS1 mRNA expression (-0.7 < r < -0.6) also function as tumor suppressors, oncogenes, or both. Our study shows that both miR-532-5p and miR-106b-5p are down-regulated and have a negative correlation with AS1 mRNA expression, which is consistent with the results of another study that showed that miR-532-5p and miR-106a-5p are significantly down-regulated in HTLV-1 asymptomatic carriers [125]. MiR-106b targets the cell cycle regulatory gene p21 (CDKN1A) and is also specifically downregulated in HIV-1 infected CD4 + T cells [126].…”

Viral Causality of Human Cancer and Potential Roles of Human Endogenous Retroviruses in the Multi-Omics Era: An Evolutionary Epidemiology Review

“…These findings underline the role of other not yet recognized molecular pathways related to the role of this miRNA (152). Recently, an sRNA-seq analysis revealed a distinct profile of miRNA expression in the PBMCs of HTLV−1 asymptomatic carriers compared to controls, a fact that may underline their role in latency and malignant hallmark development (153).…”

Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

“…These miRNAs include mmu-miR-98 that were upregulated, and mmu-miR-532 and mmu-miR-744 were downregulated in the same OVA-immunized derived offspring group and others 45 microRNAs that were differentially expressed between evaluated groups. A study suggests mmu-miR-744 as a potent type I interferon inducer [ 51 ] and mmu-miR-523 as a pro-inflammatory cytokine attenuation microRNA [ 52 ]. These observations may indicate that mmu-miR-744 and mmu-miR-523 could eventually influence the balance between IL-17/IFN-γ production, or the pro-inflammatory profile of γδT cells but, to elucidate the role of these and others microRNAs, further experiments need to be undertaken.…”