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Abstract The characteristic accumulation of late-stage differentiated CD8+ T cells is enhanced by lifelong latent cytomegalovirus (CMV) persistence, which makes it challenging to screen for subclinical biomarkers of immune aging in the elderly. We systematically identified predominantly preformed, long, noncoding RNAs (lncRNAs) as integrative biomarkers of CD8+ T cell aging in 14 elderly CMV carriers over 80 years of age. After sorting the CD28nullCD8+ T cell subset and its CD28bearingCD8+ counterpart in five nonagenarians, we profiled the differential expression of lncRNAs and genes in CD28nullCD8+ T cells via array detection. We focused on 11 differentially expressed antisense lncRNAs and cross-referenced them with previously identified age-accumulated lncRNAs to create a set of candidates in CD28nullCD8+T cells. We performed intracellular validation on the age-accumulated candidate lncRNAs paired with their antisense target genes using quantitative polymerase chain reaction (qPCR). Simultaneously, we sorted the CMV pp65 -specific CD8+ T cell subset and its counterpart from participant cells with the HLA-A-*0201 genotype. The validated age-accumulated lncRNAs in CD28nullCD8+ T cells were intracellularly cross-validated in CMV pp65 CD8+ T cells. Finally, we identified the immunity-related gene(s) that acted as potential target(s) to the cross-validated age-accumulated lncRNA(s), using bioinformatics techniques. The potential regulation of the final identified lncRNA-gene pair(s) was simultaneously predicted in two pathway-integrated networks. We concluded that expression of an age-accumulated lncRNA (NRON) was decreased, whereas that of its immunity-related target gene (NFAT) was increased, in both CD28nullCD8+ T cells and CMV pp65 CD8+ T cells of elderly individuals with persistent CMV infection. The identification of NRON as a potential biomarker suggests that NRON contributes to CMV-enhanced CD28nullCD8+ T cell aging by modulating phosphorylation and/or IL-4-dependent NFAT signaling. Highlights • Screen a subclinical biomarkers of CD8+ T cell aging which is episodically enhanced by lifelong latent cytomegalovirus (CMV) persistence in overlapped cells between CD28nullCD8+ T cells and CMV pp65 CD8+ T cells of elderly individuals with persistent CMV infection. • Systematically identify the predominantly preformed long noncoding RNA NRON as a potentially integrative biomarker for CMV-amplified CD8+ T cell accumulation during immune aging. • Predict that the reduced expression of NRON may contribute to CMV-amplified CD28nullCD8+ T cell accumulation by modulating phosphorylation and/or IL-4-dependent NFAT signaling. [ABSTRACT FROM AUTHOR]

Cancer is caused by the abnormal proliferation of local tissue cells under the control of many oncogenic factors. MicroRNAs (miRNAs) are a class of evolutionarily conserved, approximately 22-nucleotide noncoding small RNAs that influence transcriptional regulationby binding to the 3′-untranslated region of target messenger RNA. As a member of the miRNA family, miR-141 acts as a suppressor or an oncomiR in various cancers and regulates cancer cell proliferation, apoptosis, invasion, and metastasis through a variety of signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and constitutive activation of nuclear factor-κB (NF-κB). Target gene validation and pathway analysis have provided mechanistic insight into the role of this miRNA in different tissues. This review also outlines novel findings that suggest miR-141 may be useful as a noninvasive biomarker and as a therapeutic target in several cancers. • Regulatory mechanisms of miR-141 in cancer • Regulatory roles of miR-141 in various cancers • miR-141 as a tumor drug therapy • miR-141 as a drug resistance • miR-141 as a diagnostic marker of cancers [ABSTRACT FROM AUTHOR]