Epigenetic silencing of miR-181c by DNA methylation in glioblastoma cell lines

Ayala-Ortega, Erandi; Arzate-Mejía, Rodrigo G.; Pérez‐Molina, Rosario; González-Buendía, Edgar; Meier, Karin; Guerrero, Georgina; Recillas‐Targa, Félix

doi:10.1186/s12885-016-2273-6

Cited by 33 publications

(27 citation statements)

References 53 publications

(68 reference statements)

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“…Comparing normalized expression (ΔCt) of miR-181c and normalized expression (ΔCt) NOTCH2 among all of the in vitro replicates, we obtained a correlation of -0.89 (p<0.0001, df=14). These data are consistent with the direct targeting relationship between miR-181c and NOTCH2 seen in other cancers [24,25] and suggest that miR-181c directly targets NOTCH2 in endometrial cancer as well.…”

Section: Resultssupporting

confidence: 89%

“…If this is the case, then the question arises as to the mechanism through which miR-181c is down-regulated. In gastric cancers and in glioblastoma, expression of miR-181c is regulated by methylation of its promoter [24,25]. If promoter methylation is a viable mechanism through which miR-181c expression is reduced in endometrial adenocarcinomas resulting in increased NOTCH2 expression, then both miR-181c and NOTCH2 become viable therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

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Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study

Devor

Miecznikowski

Schickling

et al. 2017

Gynecologic Oncology

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Objective Endometrial cancer can be diagnosed early and cured, yet cases that recur portend a very poor prognosis with over 10,000 women succumbing to the disease every year. In this study we addressed the question of how to recognize cases likely to recur early in the course of therapy using dysregulation of tumor microRNAs (miRNAs) as predictors. Methods Using the tissue collection from Gynecologic Oncology Group Study-210, we selected and analyzed expression of miRNAs in 54 recurrent and non-recurrent cases. The three most common histologic types, endometrioid adenocarcinoma (EEA), serous adenocarcinoma (ESA) and carcinosarcoma (UCS), were analyzed as three independent sets and their miRNA expression profiles compared. Results Only one miRNA was statistically different between recurrent and non-recurrent cases, and in only one histologic type: significant down-regulation of miR-181c was observed in EEA recurrence. Using several well-known databases to assess miR-181c targets, one target of particular relevance to cancer, NOTCH2, was well supported. Using The Cancer Genome Atlas and our validation tumor panel from the GOG-210 cohort, we confirmed that NOTCH2 is significantly over-expressed in EEA. In the most relevant endometrial adenocarcinoma cell model, Ishikawa H, altering miR-181c expression produces significant changes in NOTCH2 expression, consistent with direct targeting. Conclusions Our findings suggest that increased NOTCH2 via loss of miR-181c is a significant component of EEA recurrence. This presents an opportunity to develop miR-181c and NOTCH2 as markers for early identification of high risk cases and the use of NOTCH inhibitors in the prevention or treatment of recurrent disease.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study

Devor

Miecznikowski

Schickling

et al. 2017

Gynecologic Oncology

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“…Cells originating from the same precursors tend to have a similar CTCF-binding landscape whereas cells from different lineages can have marked differences in CTCF occupancy (Prickett et al, 2013;Wang et al, 2012). DNA methylation can affect CTCF binding (Ayala-Ortega et al, 2016;Bell and Felsenfeld, 2000;Hark et al, 2000), possibly by regulating the affinity of CTCF for DNA (Hashimoto et al, 2017). However, the true extent to which DNA methylation directly affects CTCF binding is still controversial (Maurano et al, 2015).…”

Section: Ctcf Is Required For Early Vertebrate Developmentmentioning

confidence: 99%

Developing in 3D: the role of CTCF in cell differentiation

2018

Self Cite

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CTCF is a highly conserved zinc-finger DNA-binding protein that mediates interactions between distant sequences in the genome. As a consequence, CTCF regulates enhancer-promoter interactions and contributes to the three-dimensional organization of the genome. Recent studies indicate that CTCF is developmentally regulated, suggesting that it plays a role in cell type-specific genome organization. Here, we review these studies and discuss how CTCF functions during the development of various cell and tissue types, ranging from embryonic stem cells and gametes, to neural, muscle and cardiac cells. We propose that the lineage-specific control of CTCF levels, and its partnership with lineage-specific transcription factors, allows for the control of cell type-specific gene expression via chromatin looping.

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“…Of course, this assumption needs to be confirmed by further studies. Moreover, some previous reports indicated that DNA methylation can regulate microRNAs gene expression [68]. The DNA methylation profile of the miR-124 promoter region should be explored in the future.…”

Section: Discussionmentioning

confidence: 98%

CB2/miR-124 signaling down-regulate the expression of purinergic P2X4 and P2X7 receptor in dorsal spinal cord of CCI rats

Xu¹,

Yang²,

Li³

et al. 2020

Preprint

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Background: The importance of P2X purinoceptors, CB2 receptor and microRNA-124(miR-124) in spinal cord microglia to the development of neuropathic pain was demonstrated in numerous previous studies. The upregulation of P2X4 and P2X7 receptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not clear whether the expression of P2X4 and P2X7 receptors at dorsal spinal cord will be influenced by CB2 receptor or miR-124 in rats after chronic sciatic nerve injury.Methods: Chronic constriction injury (CCI) of the sciatic nerve was performed in rats to induce neuropathic pain. Tests of the mechanical withdrawal threshold (MWT) were carried out to assess the response of the paw to mechanical stimulus. The expression of miR-124, P2X4, P2X7 and CB2 receptor were detected with RT-PCR. The protein expression of P2X4, P2X7 and CB2 receptor, RhoA, ROCK1, ROCK2, p-p38MAPK and p-NF-kappaBp65 was detected with Western blotting analysis. Results: Intrathecal administration of CB2 receptor agonist AM1241 significantly attenuated CCI-induced mechanical allodynia and significantly inhibited the increased expression of P2X4 and P2X7 receptors at the mRNA and protein levels, which imply that P2X4 and P2X7 receptors expression are down-regulated by AM1241 in CCI rats. Western blot analysis showed that AM1241 suppressed the elevated expression of RhoA, ROCK1, ROCK2, p-p38MAPK and NF-κBp65 in the dorsal spinal cord induced by CCI. After administration with Y-27632 (ROCK inhibitor), SB203580 (P38MAPK inhibitor) or PDTC (NF-κB inhibitor), the levels of P2X4 and P2X7 receptors expression in the dorsal spinal cord were lower than those in CCI rats, which imply that the ROCK/P38MAPK pathway and NF-κB activation may contribute to the increased expression of P2X4 and P2X7 receptor. On the other hand, in CCI rats, AM1241 treatment evoked the increased expression of CB2 receptor and miRNA-124, which can be inhibited by intrathecal injection of CB2 receptor antagonist AM630, which indicate that the increased expression of miRNA-124 may be medicated by CB2 receptor activation. In addition, the increased expression of P2X4 and P2X7 receptors in the dorsal spinal cord of CCI rats were inhibited by miRNA-124 agomir. Furthermore, intrathecal injection of miRNA-124 agomir could efficiently inhibit the ROCK/P38MAPK pathway and NF-κB activation in CCI rats. Moreover, AM1241 treatment significantly inhibited the expression of P2X4 and P2X7 receptors, and this suppression is enhanced by pretreatment with miRNA-124 agomir. On the contrast, the inhibitory effect of AM1241 on the expression of P2X4 and P2X7 receptor can be reversed by pretreatment with miRNA-124 antagomir.Conclusions: In CCI rats, intrathecal injection of AM1241 could efficiently induce the increased expression of miRNA-124, while inhibiting the ROCK/P38MAPK pathway and NF-κB activation in dorsal spinal cord. CB2 receptor/miRNA-124 signaling induced the decreased P2X4 and P2X7 receptors expression via inhibit the ROCK/P38MAPK pathway and NF-κB activation.

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Epigenetic silencing of miR-181c by DNA methylation in glioblastoma cell lines

Cited by 33 publications

References 53 publications

Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study

Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study

Developing in 3D: the role of CTCF in cell differentiation

CB2/miR-124 signaling down-regulate the expression of purinergic P2X4 and P2X7 receptor in dorsal spinal cord of CCI rats

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