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MicroRNA-129 Inhibits Glioma Cell Growth by Targeting CDK4, CDK6, and MDM2.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2019-12-12 , DOI: 10.1016/j.omtn.2019.11.033
Atieh Moradimotlagh 1 , Ehsan Arefian 1 , Rezvan Rezazadeh Valojerdi 1 , Shokoofeh Ghaemi 1 , Fatemeh Jamshidi Adegani 2 , Masoud Soleimani 3
Affiliation  

Glioblastoma is the most common malignant primary brain tumor among adults and one of the most lethal cancers. It is characterized by the deregulation of signaling pathways involving proliferation, growth, survival, and other factors. MicroRNAs (miRNAs) play a role in the regulation of genes by affecting the 3′ untranslated region (UTR) of mRNA and affect many cell functions. The present study showed that miR-129 decreased the expression of retinoblastoma and p53 signaling pathways’ genes, including CDK4, CDK6, and MDM2. The real-time PCR data indicated that expression of CDK4 in U251 and U87 cell lines declined by 69.8% and 47% (p < 0.05), respectively, and expression of CDK6 and MDM2 in U251 cells decreased by 55.3% (p < 0.0001) and 34.7% (p < 0.05), respectively. Luciferase assays confirmed that overexpression of miR-129 decreased the expression of the CDK4 gene by 58.9% (p < 0.01), CDK6 by 35.7% (p < 0.0001), and MDM2 by 49% (p < 0.001). Moreover, cell cycle assays showed a decrease of the G2-phase population to 10% and pre-G2 arrest in U87 cells (p < 0.05). Additionally, wound healing assays indicated that miR-129 overexpression inhibits cell growth of glioblastoma cells. These findings introduced novel targets for miR-129 in glioblastoma cells.



中文翻译:

MicroRNA-129通过靶向CDK4,CDK6和MDM2抑制胶质瘤细胞生长。

胶质母细胞瘤是成年人中最常见的恶性原发性脑肿瘤,也是最致命的癌症之一。其特征在于涉及增殖,生长,存活和其他因素的信号传导通路的失控。微小RNA(miRNA)通过影响mRNA的3'非翻译区(UTR)并影响许多细胞功能,从而在基因调控中发挥作用。本研究表明,miR-129降低了视网膜母细胞瘤的表达和p53信号通路的基因,包括CDK4CDK6MDM2。实时PCR数据表明CD251在U251和U87细胞系中的表达分别下降了69.8%和47%(p <0.05),而CDK6MDM2的表达则下降了。在U251细胞中,分别降低了55.3%(p <0.0001)和34.7%(p <0.05)。萤光素酶测定证实,miR-129的过表达使CDK4基因的表达降低58.9%(p <0.01),使CDK6的表达降低35.7%(p <0.0001),而使MDM2的表达降低49%(p <0.001)。此外,细胞周期分析显示U87细胞中G 2期群体减少至10%,且G 2前阻滞(p <0.05)。另外,伤口愈合试验表明miR-129过表达抑制胶质母细胞瘤细胞的细胞生长。这些发现为胶质母细胞瘤细胞中的miR-129引入了新的靶标。

更新日期:2019-12-12
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