Stepwise detection and evaluation reveal miR-10b and miR-222 as a remarkable prognostic pair for glioblastoma

Abstract

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.

Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy

“…Table 3 summarizes the previously published data of survival analyses of GBM patients for miR-221/222. For the TCGA cohort, a correlation between miR-221/222 expression and OS had previously been reported, demonstrating a negative prognostic impact; however, Delfino et al showed a positive prognostic correlation of miR-221 in a subgroup of patients who received RT [ 45 , 46 , 47 ]. Apart from TCGA, Li et al quantified the expression level of miR-221/222 in 54 GBM samples by qRT-PCR and confirmed the correlation between high miR-221/222 expression and poor outcome [ 30 ].…”

LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

“…MiRNAs are highly conserved across species, and regulate gene expression by binding to the 3′-untranslated region (3′-UTR) of target mRNAs. More and more miRNAs were demonstrated to play important roles in glioma [26][27][28].…”

Global microRNA profiling identified miR‐10b‐5p as a regulator of neurofibromatosis 1 (NF1)‐glioma migration

“…A meta-analysis of 19 studies of various sporadic tumour types including colorectal cancer, breast cancer, pancreatic cancer, nonsmall cell lung carcinoma and gliomas suggest a correlation between miR-10b overexpression and decreased overall survival [21]. Prior functional experiments in glioma cell lines have documented a role for miR-10b in radiation resistance [22], proliferation [23] and inhibition of apoptosis [24]. Focusing on NF1-associated tumours, miR-10b has been found to be overexpressed in MPNST [25], particularly NF1-associated MPNST where neurofibromin itself may be a target [26].…”