MiR-450a-5p strengthens the drug sensitivity of gefitinib in glioma chemotherapy via regulating autophagy by targeting EGFR.

Abstract

Glioma reported to be refractory to EGFR tyrosine kinase inhibitor is the most common malignant tumor in central nervous system. Our research showed the low expression of miR-450a-5p and high expression of EGFR in glioma tissues. MiR-450a-5p was also observed to synergize with gefitinib to inhibit the proliferation, migration and invasion and induce the apoptosis and autophagy of glioma cells. Furthermore, miR-450a-5p was demonstrated to target 3'UTR of EGFR, and regulated EGFR-induced PI3K/AKT/mTOR signaling pathway. Moreover, the above effects induced by miR-450a-5p in glioma cells were reversed by WIPI1 silencing. The inhibition role of miR-450a-5p on glioma growth was also confirmed in vivo by subcutaneous and intracranial tumor xenografts. Therefore, we conclude that miR-450a-5p synergizes with gefitinib to inhibit the glioma tumorigenesis through inducing autophagy by regulating the EGFR-induced PI3K/AKT/mTOR signaling pathway, thereby enhancing the drug sensitivity of gefitinib.

• Authors: Yu Liu, Liang Yang, Fan Liao, Wei Wang, Zhi-Fei Wang
• Journal: Oncogene (Oncogene) Vol. 39 Issue 39 Pg. 6190-6202 (09 2020) ISSN: 1476-5594 [Electronic] England
• PMID: 32820249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• MIRN450 microRNA, human
• MicroRNAs
• MTOR protein, human
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• PPM1D protein, human
• Protein Phosphatase 2C
• Gefitinib

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Brain Neoplasms (drug therapy, genetics, metabolism)
• ErbB Receptors (genetics, metabolism)
• Gefitinib (pharmacology)
• Glioma (drug therapy, genetics, metabolism, pathology)
• Humans
• Mice
• MicroRNAs (biosynthesis, genetics, metabolism)
• Neoplasm Metastasis
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Phosphatase 2C (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Xenograft Model Antitumor Assays