Targeting strategies on miRNA-21 and PDCD4 for glioblastoma

(i) miR-21 downregulation increased GBM apoptosis, decreased cell proliferation, and increased G0/G1 cell cycle arrest. (ii) Inhibition of miR-21 resulted in decreased expression of EGFR, activation of AKT, as well as activation of cell cycle regulator cyclin D1, apoptosis inhibitor Bcl-2, and STAT3. (iii) miR-21 has also been shown to regulate GBM chemotherapeutic resistance, invasion, and apoptosis. (iv) miR-21, PDCD4, STAT3 are validated targets for cancer therapies, targeting therapeutic strategy for these transcription factors through small molecular drugs that inhibit miR-21 expression that are effective in glioblastoma. Ultimately, drugs that can target regulators of the STAT3/miR-21 system can promote final degradation of miR-21 in brain tumor cells. (v) Pathways downstream of receptor tyrosine kinases like PI3K/Akt/mTOR that indirectly control by miR-21 are often overexpressed or altered in brain tumors. Sirt2 is critical in human glioma via NF-κB-miR-21 pathway and Sirt2 activator may serve as regulating factor of miR-21 for glioma therapy.184