TY  - EJOU
AU  - Chao, Chun-Nun 
AU  - Fang, Chiung-Yao 
AU  - Hou, Chia-Hsin 
AU  - Yang, Jen-Tsung 
AU  - Wu, Yu-Ping 
AU  - Chen, Jui-Chieh 

TI  - miR-152-3p Overcomes Temozolomide Resistance in Glioblastoma by Targeting TGF-α and Enhancing Apoptosis
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Objectives:</b> Temozolomide (TMZ) resistance remains a major challenge in glioblastoma (GBM) treatment. This study investigated the role of miR-152-3p and its downstream target, transforming growth factor-α (TGF-α), in regulating TMZ sensitivity in GBM. <b>Methods:</b> Public GEO and CGGA datasets were analyzed to evaluate the expression and prognostic significance of miR-152-3p. TMZ-resistant GBM cell lines (U87MGR and DBTRG-05MGR) were established by continuous TMZ exposure. Gain- and loss-of-function experiments were performed using miR-152-3p mimics and inhibitors. Cell viability, apoptosis, and TGF-α expression were assessed by MTT, qRT-PCR, and Western blot analyses. <b>Results:</b> miR-152-3p expression was significantly decreased in recurrent GBM and was associated with poor overall survival. TMZ-resistant GBM cells exhibited lower miR-152-3p expression than parental cells. Bioinformatic analyses identified TGF-α as a potential target of miR-152-3p. Overexpression of miR-152-3p suppressed TGF-α expression, reduced cell viability, and enhanced TMZ-induced apoptosis in resistant GBM cells. TGF-α knockdown similarly restored TMZ sensitivity. Conversely, inhibition of miR-152-3p increased TGF-α expression and attenuated TMZ-induced apoptotic signaling in TMZ-sensitive M059K cells. <b>Conclusion:</b> Together, our findings demonstrate that the miR-152-3p/TGF-α axis plays a critical role in regulating TMZ sensitivity in GBM, and targeting this pathway may represent a therapeutically relevant signaling axis to overcome chemoresistance.
KW  - Glioblastoma (GBM); temozolomide (TMZ); drug resistance; MiR-152-3p; transforming growth factor-alpha (TGF-α)

DO  - 10.32604/or.2026.083962