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

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 g...

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Bibliographic Details
Published in:International journal of biological sciences 2020-01, Vol.16 (16), p.3200-3209
Main Authors: Zhang, Junfeng, Deng, Mengsheng, Tong, Haipeng, Xue, Wei, Guo, Yu, Wang, Jianmin, Chen, Lizhao, Wang, Shunan
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers
Brain
Brain cancer
Brain tumors
Cancer
Cell culture
Cell growth
Chromosome 3
Gene expression
Genomes
Glioma cells
Homeobox
Invasiveness
Laboratory animals
Medical prognosis
MicroRNAs
Next-generation sequencing
Phenotypes
Plasmids
Research Paper
Transfection
Tumors
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Summary: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 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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.51293