Intracellular Modulation, Extracellular Disposal and Serum Increase of MiR-150 Mark Lymphocyte Activation

Candia, Paola de; Torri, A; Gorletta, Tatiana; Fedeli, Maya; Bulgheroni, Elisabetta; Cheroni, Cristina; Marabita, Francesco; Crosti, Mariacristina; Moro, Monica; Pariani, Elena; Romanò, Luisa; Esposito, Susanna; Mosca, Fabio; Rossetti, Grazisa; Rossi, Riccardo L.; Geginat, Jens; Casorati, Giulia; Pagani, Massimiliano; Abrignani, Sergio

doi:10.1371/journal.pone.0075348

Cited by 68 publications

(83 citation statements)

References 32 publications

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“…Finally, it maybe resulted from the selective package and secretion process of circulating miRNA. Previous reports showed that the expression pattern of some miRNAs in intracellular was contrary to that in extracellular owing to the selective disposal363738.…”

Section: Discussionmentioning

confidence: 94%

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

Chen

Pang

et al. 2016

Sci Rep

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Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study. Two types of osteoporosis models were used like as mechanical unloading and estrogen deficiency. Through a large-scale screening using microarray, qPCR validation and statistical algorithms, we first identified miR-25-3p as a suitable reference gene for both type of osteoporosis, which also showed stability during the differentiation processes of osteoblast and osteoclast. Then 15 serum miRNAs with differential expression in OVX rats were identified by microarray and qPCR validation. We further detected these 15 miRNAs in postmenopausal women and bedrest rhesus monkeys and evaluated their diagnostic value by ROC analysis. Among these miRNAs, miR-30b-5p was significantly down-regulated in postmenopausal women with osteopenia or osteoporosis; miR-103-3p, miR-142-3p, miR-328-3p were only significantly decreased in osteoporosis. They all showed positive correlations with BMD. Except miR328-3p, the other three miRNAs were also declined in the rhesus monkeys after long-duration bedrest. Their AUC values (all >0.75) proved the diagnostic potential. Our results provided a reliable normalization reference gene and verified a group of circulating miRNAs as non-invasive biomarkers in the detection of postmenopausal- and mechanical unloading- osteoporosis.

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Section: Discussionmentioning

confidence: 94%

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

Chen

Pang

et al. 2016

Sci Rep

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“…In line with these findings, in vivo studies show that miR-150 is released in the external environment after T cell activation, and this may cause an increase of its blood levels during immune system stimulation. 38 Further experiments aimed at clarifying the precise role of miR-150 in human melanoma immunity are warranted.…”

Section: Discussionmentioning

confidence: 99%

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma

et al. 2017

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Melanoma is a devastating disease with few therapeutic options in the advanced stage and with the urgent need of reliable biomarkers for early detection. In this context, circulating microRNAs are raising great interest as diagnostic biomarkers. We analyzed the expression profiles of 21 selected microRNAs in plasma samples from melanoma patients and healthy donors to identify potential diagnostic biomarkers. Data analysis was performed using global mean normalization and NormFinder algorithm. Linear regression followed by receiver operating characteristic analyses was carried out to evaluate whether selected plasma miRNAs were able to discriminate between cases and controls. We found five microRNAs that were differently expressed among cases and controls after Bonferroni correction for multiple testing. Specifically, miR-15b-5p, miR-149-3p, and miR-150-5p were up-regulated in plasma of melanoma patients compared with healthy controls, while miR-193a-3p and miR-524-5p were down-regulated. Receiver operating characteristic analyses of these selected microRNAs provided area under the receiver operating characteristic curve values ranging from 0.80 to 0.95. Diagnostic value of microRNAs is improved when considering the combination of miR-149-3p, miR-150-5p, and miR-193a-3p. The triple classifier had a high capacity to discriminate between melanoma patients and healthy controls, making it suitable to be used in early melanoma diagnosis.

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“…It is, therefore, plausible that cellular export serves an auxiliary route to efficient elimination of undesired miRNAs. In line with this, selective exosomal disposal of miR150 was recently proposed as a rapid means to regulate gene expression during lymphocyte activation (43). Thus, a balance of "intracellular active" versus "exocytosis inactive" miRNAs is likely influencing the transcriptome as a whole.…”

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confidence: 86%

Cellular Disposal of miR23b by RAB27-Dependent Exosome Release Is Linked to Acquisition of Metastatic Properties

et al. 2014

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Exosomes are small secreted vesicles that can transfer their content to recipient cells. In cancer, exosome secretion has been implicated in tumor growth and metastatic spread. In this study, we explored the possibility that exosomal pathways might discard tumor-suppressor miRNA that restricts metastatic progression. Secreted miRNA characterized from isogenic bladder carcinoma cell lines with differing metastatic potential were uncoupled from binding to target transcripts or the AGO2-miRISC complex. In metastatic cells, we observed a relative increase in secretion of miRNA with tumor-suppressor functions, including miR23b, miR224, and miR921. Ectopic expression of miR23b inhibited invasion, anoikis, angiogenesis, and pulmonary metastasis. Silencing of the exocytotic RAB family members RAB27A or RAB27B halted miR23b and miR921 secretion and reduced cellular invasion. Clinically, elevated levels of RAB27B expression were linked to poor prognosis in two independent cohorts of patients with bladder cancer. Moreover, highly exocytosed miRNA from metastatic cells, such as miR23b, were reduced in lymph node metastases compared with patient-matched primary tumors and were correlated with increments in miRNA-targeted RNA. Taken together, our results suggested that exosomemediated secretion of tumor-suppressor miRNA is selected during tumor progression as a mechanism to coordinate activation of a metastatic cascade. Cancer Res; 74(20); 5758-71. Ó2014 AACR.

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Intracellular Modulation, Extracellular Disposal and Serum Increase of MiR-150 Mark Lymphocyte Activation

Cited by 68 publications

References 32 publications

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma

Cellular Disposal of miR23b by RAB27-Dependent Exosome Release Is Linked to Acquisition of Metastatic Properties

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