miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis

Aberrant activation of STAT3 drives glioma tumorigenesis, but the critical effector mechanisms involved are not fully understood. Here we report the finding that miR-182-5p is a critical mediator of STAT3 in this process. Bioinformatics analyses determined that tumor suppressor protocadherin-8 (PCDH8) is a candidate target gene of miR-182-5p, which was found to negatively regulate PCDH3 by directly targeting its 3'-untranslated region. Notably, PCDH8 silencing was sufficient to drive the proliferative and invasive capabilities of glioma cells. Further, PCDH8 silencing or miR-182-5p mimetics were sufficient to reverse the effects of STAT3 inhibition in vitro and in vivo, either pharmacologically by treatment with the small molecule inhibitor WP1066 or genetically by silencing STAT3. Clinically, expression levels of PCDH8 in glioblastoma specimens correlated inversely with levels of phosphorylated STAT3 or miR-182-5p. Taken together, our results defined a novel STAT3/miR-182-5p/PCDH8 signaling axis with a critical role in glioma tumorigenesis, offering potential therapeutic opportunities in this disease.