MiR-181b modulates chemosensitivity of glioblastoma multiforme cells to temozolomide by targeting the epidermal growth factor receptor

Abstract

Temozolomide (TMZ) is a promising chemotherapeutic agent to treat Glioblastoma multiforme (GBM). However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells' resistance to TMZ are not fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. Recently, miRNAs have been discovered to play important roles in drug resistance. A previous study showed that miR-181b in involved in glioma tumorigenesis. Thus, it would be valuable to explore the functions and mechanisms of miR-181b in regulating GMB cells' sensitivity to TMZ. In this study, quantitative real-time reverse transcription PCR (qRT-PCR) data indicated that miR-181b was significantly downregulated in recurrent GBM tissues compared with initial GBM tissues. We also found that miR-181b overexpression increased the chemo-sensitivity of GBM cells to TMZ and potentiated TMZ-induced apoptosis in vitro and in vivo. Moreover, we demonstrated that the epidermal growth factor receptor (EGFR) was a direct target of miR-181b: restoration of EGFR rescued the inhibitory effects of miR-181b and TMZ treatment. Taken together, our data support strongly an important role for miR-181b in conferring TMZ resistance by targeting EGFR expression.

Keywords: Epidermal growth factor receptor; Glioblastoma multiforme; MiR-181b; Temozolomide.