miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.
miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.
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miRNA-194- 3 p抑制胶质瘤中的NF-κB以减弱iPSC基因和前神经向间质转化
DOI：
10.1016/j.isci.2023.108650
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发表时间：
2024-01-19
期刊：
影响因子：
5.8
通讯作者：
Palanichamy, Kamalakannan
中科院分区：
文献类型：
--
作者：
Jacob, John Ryan;Singh, Rajbir;Okamoto, Masa;Chakravarti, Arnab;Palanichamy, Kamalakannan
严重的肿瘤异质性驱动胶质母细胞瘤（GBM）的侵袭性和治疗难治性。虽然限制GBM异质性提供了有希望的治疗潜力，但调节GBM可塑性的潜在机制仍然知之甚少。我们利用14个患者来源的细胞系和4个市售细胞系来揭示miR-194- 3 p作为GBM中干性和转录亚型的关键表观遗传决定因素。我们证明miR-194- 3 p降解TAB 2，这是NF-κB活性的重要介质，降低NF-κB转录活性。miR-194- 3 p过表达或TAB 2沉默后NF-κB活性的丧失降低了诱导多能干细胞（iPSC）基因的表达，抑制了致癌性IL-6/STAT 3信号传导轴，抑制了与前神经亚型相关的间充质转录亚型，并诱导了胶质瘤干细胞（GSC）向单层（ML）表型的分化。miR-194- 3 p/TAB 2/NF-κB信号轴作为表观遗传开关调节GBM可塑性，靶向该信号轴代表限制GBM中转录异质性的潜在策略。GSC抑制miR-194- 3 p促进TAB 2介导的NF-κB活化GBM利用miR-194- 3 p转录调节iPSC因子和肿瘤亚型破坏miR-194- 3 p/TAB 2/NF-κB信号轴抑制PMT miR-194- 3 p/TAB 2/NF-κB轴的遗传消融减少肿瘤异质性神经科学;分子神经科学;干细胞研究;癌症
Severe tumor heterogeneity drives the aggressive and treatment refractory nature of glioblastomas (GBMs). While limiting GBM heterogeneity offers promising therapeutic potential, the underlying mechanisms that regulate GBM plasticity remain poorly understood. We utilized 14 patient-derived and four commercially available cell lines to uncover miR-194-3p as a key epigenetic determinant of stemness and transcriptional subtype in GBM. We demonstrate that miR-194-3p degrades TAB2, an important mediator of NF-κB activity, decreasing NF-κB transcriptional activity. The loss in NF-κB activity following miR-194-3p overexpression or TAB2 silencing decreased expression of induced pluripotent stem cell (iPSC) genes, inhibited the oncogenic IL-6/STAT3 signaling axis, suppressed the mesenchymal transcriptional subtype in relation to the proneural subtype, and induced differentiation from the glioma stem cell (GSC) to monolayer (ML) phenotype. miR-194-3p/TAB2/NF-κB signaling axis acts as an epigenetic switch that regulates GBM plasticity and targeting this signaling axis represents a potential strategy to limit transcriptional heterogeneity in GBMs. GSCs suppress miR-194-3p to promote TAB2 mediated NF-κB activation GBMs utilize miR-194-3p to transcriptionally regulate iPSC factors and tumor subtypes Disrupting miR-194-3p/TAB2/NF-κB signaling axis inhibits PMT Genetic ablation of miR-194-3p/TAB2/NF-κB axis diminishes tumor heterogeneity Neuroscience; Molecular neuroscience; Stem cells research; Cancer
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DOI：
10.1016/j.biocel.2017.12.020
发表时间：
2018-03
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Bennett J;Capece D;Begalli F;Verzella D;D'Andrea D;Tornatore L;Franzoso G
通讯作者：
Franzoso G
影响因子：
4.6
作者：
Tang J;He D;Yang P;He J;Zhang Y
通讯作者：
Zhang Y
分析前神经向间质转化，识别神经胶质瘤中的 lncRNA 特征
影响因子：
7.4
作者：
Liang Q;Guan G;Li X;Wei C;Wu J;Cheng P;Wu A;Cheng W
通讯作者：
Cheng W
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K