期刊
ONCOGENE
卷 38, 期 33, 页码 6142-6157出版社
SPRINGERNATURE
DOI: 10.1038/s41388-019-0867-6
关键词
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资金
- National Key Research and Development Plan [2016YFC0902500]
- National Natural Science Foundation of China [81702972, 81572701, 81772666]
- Special Fund Project of Translational Medicine in the Chinese-Russian Medical Research Center [CR201417]
- Fundamental Research Funds for the Central Universities [2572018BH01]
- Specialized Personnel Start-up Grant [41113237]
Despite the existence of many clinical and molecular factors reported that contribute to survival in glioblastoma, prevailing studies fell into partial or local feature selection for survival analysis. We proposed a feature selection strategy including not only joint covariate detection but also its evaluations, and performed it on miRNA expression profiles with glioblastoma. MiR-10b and miR-222 were selected as the most significant two-dimensional feature. Crucially, we integrated in vitro experiments on GBM cells and in vivo studies on a mouse model of human glioma to elucidate the synergistic effects between miR-10b and miR-222. Inhibition of miR-10b and miR-222 strongly suppress GBM cells growth, invasion, and induce apoptosis by co-targeting PTEN and leading to activation of p53 ultimately. We also demonstrated that miR-10b and miR-222 co-target BIM to induce apoptosis independent of p53 status. The results define mir-10b and mir-222 important roles in gliomagenesis and provided a reliable survival analysis strategy.
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