A miR-150/TET3 pathway regulates the generation of mouse and human non-classical monocyte subset

Selimoglu-Buet, Dorothée; Rivière, Julie; Ghamlouch, Hussein; Bencheikh, Laura; Lacout, Catherine; Morabito, Margot; Diop, M’Boyba; Meurice, Guillaume; Breckler, Marie; Chauveau, Aurélie; Debord, Camille; Debeurme, Franck; Itzykson, Raphaël; Chapuis, Nicolas; Willekens, Christophe; Wagner-Ballon, Orianne; Bernard, Olivier A.; Droin, Nathalie; Solary, Éric

doi:10.1038/s41467-018-07801-x

Cited by 38 publications

(33 citation statements)

References 70 publications

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“…Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene. Recent studies showed that TETs were direct targets of multiple microRNAs [31][32][33][34]; however, there are few studies on the regulation of microRNAs by TETS. In the present study, we found that TET3 could not only promote the expression of miR-145, but also inhibit the Warburg effect of ovarian cancer cells through miR-145.…”

Section: Discussionmentioning

confidence: 99%

Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells

Zou

Pei

et al. 2021

J. Cancer

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Background: Berberine, as an alkaloid, has a significant antitumor effect, but its mechanism in tumor metabolism, especially the Warburg effect has not been elucidated. Objectives: To study the molecular mechanism of berberine regulating the Warburg effect in ovarian cancer cells. Methods: Treatment by berberine in SKOV3 and 3AO cells or inhibited by miR-145 inhibitor transfection in berberine-treated cells to examine the changes in HK2 expression, glucose consumption and lactate production. The methylation status in the promoter region of pre-miR-145 gene was examined by bisulfite sequencing. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-145 to HK2. Finally, the expression of TET3 in ovarian cancer was investigated by quantitative real-time PCR and immunohistochemistry. Results: We found berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly. Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene. We further found that TET3 expression was negatively correlated with clinical stage and pathological grade. Conclusions: Our results revealed berberine increased the TET3-mediated demethylation and promoted the suppression of miR-145 on HK2 to antagonize the Warburg effect of ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells

Zou

Pei

et al. 2021

J. Cancer

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“…Functionally, miR-150 controls the transcription factor transcriptional activator Myb, which affects the development and immune response of lymphocytes [56]. In monocytes, miR-150 regulates the generation of non-classical monocyte subsets, with miR-150 being upregulated in non-classical monocytes and downregulated in classical monocytes [57]. Increased differentiation of monocytes towards the non-classical phenotype has been associated with survival in sepsis [58].…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Braza-Boïls

Barwari

Gutmann

et al. 2020

IJMS

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There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y 12 inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated effects were altered by P2Y 12 inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y 12 inhibition. While P2Y 12 inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia.

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“…The genes regulating this transition in humans are continuing to be defined. In adult CMML, the mechanistic basis of the high classical monocyte content was recently investigated 16 . The evidence suggests that hypermethylation of miR‐150 and secondary downregulation of TET3 gene expression may be responsible for the higher proportion of classical monocytes; importantly this effect was reversed using hypomethylating agents in responding patients.…”

Section: Discussionmentioning

confidence: 99%

CD14/16 monocyte profiling in juvenile myelomonocytic leukemia

Gadgeel

Bagla

Buck

et al. 2020

Pediatric Blood & Cancer

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Monocyte subset analysis by flow cytometry has been shown to be a useful diagnostic tool in chronic myelomonocytic leukemia in adults. An increase in the classical monocyte fraction (CD14++/CD16−) greater than 94.0% of total monocytes is considered highly sensitive and specific in distinguishing chronic myelomonocytic leukemia from other myeloproliferative disorders. In a pilot study of juvenile myelomonocytic leukemia cases, we noted that CD14++/CD16− monocyte fraction was >95% in de novo juvenile myelomonocytic leukemia (JMML) with somatic PTPN11 mutations but normal in those with monosomy 7 or Noonan syndrome. Monocyte subgroup profiling by itself is not diagnostic of JMML but may distinguish molecular subgroups within JMML.

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A miR-150/TET3 pathway regulates the generation of mouse and human non-classical monocyte subset

Cited by 38 publications

References 70 publications

Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells

Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

CD14/16 monocyte profiling in juvenile myelomonocytic leukemia

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