A novel miR-7156-3p-HOXD13 axis modulates glioma progression by regulating tumor cell stemness.

A novel miR-7156-3p-HOXD13 axis modulates glioma progression by regulating tumor cell stemness.
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新型 miR-7156-3p-HOXD13 轴通过调节肿瘤细胞干性来调节神经胶质瘤进展

DOI:
10.7150/ijbs.51293
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发表时间:
2020
影响因子:
9.2
通讯作者:
Wang S
Wang S
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang J;Deng M;Tong H;Xue W;Guo Y;Wang J;Chen L;Wang S

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恶性神经胶质瘤是成人最常见的脑肿瘤。尽管抗胶质瘤治疗取得了巨大进展,导致临床结局显著改善,但肿瘤复发仍然是死亡的主要原因。癌细胞干性和侵袭性的增加与胶质瘤进展相关。通过检索Cancer Genome Atlas,我们发现miR-7156- 3 p在胶质瘤组织中的表达与正常脑组织相比显著降低,并且miR-7156- 3 p的降低水平与胶质瘤分级和患者生存率密切相关。临床研究一致证实miR-7156- 3 p与胶质瘤分级呈负相关。细胞培养和动物实验显示,抑制miR-7156- 3 p有效地刺激胶质瘤细胞的干细胞性、侵袭和生长。相反,miR-7156- 3 p的增加抑制了这些表型。通过下一代测序结合靶点预测方法,确定同源框D13(HOXD 13)为miR-7156- 3 p的靶基因,并通过荧光素酶报告基因分析和细胞转染实验进一步验证。另外的体外和动物实验表明,miR-7156- 3 p通过介导HOXD 13调节胶质瘤细胞的干性、侵袭和生长。总之,我们的研究结果提供了新的见解调节胶质瘤的干性和侵袭性,并可能提出一个潜在的策略,抗胶质瘤治疗。此外,miR-7156- 3 p可作为临床实践中预测胶质瘤进展的候选生物标志物。
Malignant glioma is the most common brain tumor in adults. Despite the great advances in anti-glioma treatments which have led to significant improvement in clinical outcomes, tumor recurrence remains the major cause of mortality. Increased cancer cell stemness and invasiveness are correlated with glioma progression. By searching the Cancer Genome Atlas, we showed that the expression of miR-7156-3p is significantly decreased in glioma tissues compared to the normal brain, and the decreased level of miR-7156-3p is closely correlated with glioma grade and patient survival. Clinical study consistently confirmed that miR-7156-3p is negatively correlated with glioma grade. Cell culture and animal experiments revealed that inhibition of miR-7156-3p effectively stimulates glioma cell stemness, invasion, and growth. In contrast, the augmentation of miR-7156-3p inhibits these phenotypes. Using Next-generation sequencing combined with target prediction approach, Homeobox D13 (HOXD13) is identified as the target gene of miR-7156-3p and further validated by luciferase reporter assay and cell transfection experiments. Additional in vitro and animal experiments demonstrated that miR-7156-3p regulates glioma cell stemness, invasion, and growth by mediating HOXD13. In conclusion, our findings provide new insight into the regulation of glioma stemness and invasiveness and may propose a potential strategy for anti-glioma treatment. Moreover, miR-7156-3p may serve as a candidate biomarker for predicting glioma progression in clinical practice.
靶向 E2F1 的 miRNA-329 抑制神经胶质瘤细胞的细胞增殖
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发表时间: 2013-07-17
影响因子: 7.4
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影响因子: 8
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