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miR‑146b‑5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6.
- Source :
-
Oncology reports [Oncol Rep] 2017 Nov; Vol. 38 (5), pp. 2941-2950. Date of Electronic Publication: 2017 Sep 19. - Publication Year :
- 2017
-
Abstract
- Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR‑146b‑5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR‑146b‑5p in temozolomide resistance remains unclear. In the present study, we successfully generated U87 and U251‑TR cells, and found that miR‑146b‑5p was downregulated in TR cells. Overexpression of miR‑146b‑5p restored sensitivity of U87/U251‑TR cells to TMZ by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6). The levels of TRAF6 were inversely related to miR‑146b‑5p levels, and overexpression of TRAF6 in miR‑146b‑5p‑OE cells enhanced the resistance against TMZ. Moreover, temozolomide-resistant GBM cells had a higher level of phosphorylated protein kinase B (AKT) and P65. Overexpression of miR‑146b‑5p or TRAF6 knockdown significantly decreased the level of p‑AKT and p‑p65. Collectively, our data demonstrated that miR‑146b‑5p, as a tumor suppressor, mediated temozolomide resistance in GBM cells through negatively regulating TRAF6 expression, indicating that miR‑146b‑5p and its targeted genes would be potential therapeutic targets for glioma therapy.
- Subjects :
- Animals
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Dacarbazine administration & dosage
Disease-Free Survival
Drug Resistance, Neoplasm genetics
Female
Gene Expression Regulation, Neoplastic drug effects
Glioblastoma genetics
Glioblastoma pathology
Humans
Intracellular Signaling Peptides and Proteins
Male
Mice
Neoplasm Recurrence, Local drug therapy
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local pathology
Signal Transduction drug effects
Temozolomide
Xenograft Model Antitumor Assays
Dacarbazine analogs & derivatives
Glioblastoma drug therapy
MicroRNAs genetics
TNF Receptor-Associated Factor 6 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 38
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 29048680
- Full Text :
- https://doi.org/10.3892/or.2017.5970