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.
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.
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.
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).
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.
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.
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.