Taken together, our results suggest that miR-182 could be a valuable marker of glioma progression and that high miR-182 expression is associated with poor overall survival in patients with malignant glioma.
The concentration of miRNA-182 in glioma patients was found to be 3.1 times as high as that in healthy persons, a conclusion in excellent agreement with a separate qPCR measurement of the expression level.
Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neuro-developmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM. miR-182 sensitized glioma cells to TMZ-induced apoptosis, promoted glioma initiating cell (GIC) differentiation, and reduced tumor cell proliferation via knockdown of Bcl2L12, c-Met and HIF2A.
Our findings showed that the level of circulating miR-182 in glioma patients was higher than that in healthy controls (P<0.001), which was significantly associated with KPS score (P=0.025) and WHO grade (P<0.001).
These findings reveal that the STAT3/miR-182-5p/PCDH8 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioma.
In addition, miR-182 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) was required in the regulation of UCA1 induced glioma cell proliferation.
The feasibility of the method for sensitive determination of miRNA-182 and miRNA-381 from serum samples of glioma patients at different stages was demonstrated.
In this study, lncRNA UCA1/miR-182 axis has been regarded as a nodal driver of glioma invasion mediated by GB-associated stromal cells (GASCs) and GASC-secreted chemokine CXCL14.
Furthermore, high expression of miR-182-5p and low expression of <i>SESN2</i> mRNA tend to be associated with longer survival of glioma or lung cancer patients using public available gene expression datasets and online tools for prediction of clinical outcomes.