BACH1 Promotes Temozolomide Resistance in Glioblastoma through Antagonizing the Function of p53

Nie, Er; Jin, Xin; Wu, Weining; Yu, Tianfu; Zhou, Xu; Zhi, Tongle; Shi, Zhumei; Zhang, Junxia; Liu, Ning; You, Yongping

doi:10.1038/srep39743

Cited by 30 publications

(22 citation statements)

References 41 publications

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“…Moreover, knockdown of miR-141-3p enhanced the chemosensitivity of human glioma cells to TMZ treatment and induced glioma cell apoptosis. Some mechanisms of p53 mutation or not influencing temozolomide resistance has been demonstrated in our another research article and some other research articles which support our results [ 40 , 41 ]. Of course, p53 is not the only way to affect temozolomide resistance in glioma, some ways which independent of p53 mutation or not has been found as indicated [ 21 ].…”

Section: Discussionsupporting

confidence: 91%

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

Zhou

Zeng

et al. 2017

Oncotarget

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Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro. Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R2=0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future.

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Section: Discussionsupporting

confidence: 91%

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

Zhou

Zeng

et al. 2017

Oncotarget

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“…This is supported by decreased c-myc and increased p53 expression, since both have been suggested to regulate TMZ sensitivity (5,26). For example, BACH1 promotes TMZ resistance in glioblastoma by antagonizing p53 function (27).…”

Section: Discussionmentioning

confidence: 95%

Identification of WISP1 as a novel oncogene in glioblastoma

Jiang

Zhang

et al. 2017

International Journal of Oncology

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Glioblastoma is the most common and aggressive primary brain tumor and has a high mortality in humans. However, mechanisms and factors involved in the progression of glioblastoma remain elusive. WISP1 (WNT1 inducible signaling pathway protein 1), has been suggested to be a critical regulator of cancer development. The aim of this study was to investigate the role of WISP1 in regulating the progression of glioblastoma. Clinicopathological characteristics of glioblastoma were assessed, and higher levels of WISP1 were positively associated with advanced clinical stage and a poor prognosis. Consistently, WISP1 expression was significantly upregulated in glioblastoma tissue and cell lines compared with normal tissue and cells. Additionally, inhibition of WISP1 greatly suppressed cell proliferation, migration, and invasion and promoted apoptosis and cell cycle arrest of glioblastoma cells. Further study indicated that downregulation of WISP1 suppressed cell proliferation associated with the gene expression of c‑myc and cyclin D1 and cellular signaling such as through the ERK pathway, while inhibiting epithelial-mesenchymal transition and MMP9. Finally, knockdown of WISP1 markedly suppressed in vivo tumor growth and sensitized glioblastoma cells to temozolomide. This study identified WISP1 as an oncogene in glioblastoma and suggests that WISP1 may serve as a potential molecular marker and treatment target for glioblastoma.

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“…Hierarchical bi‐clustering analysis indicated significant gene signatures in TRIB2 High /MAP3K1High GBM compared withTRIB2 Low /MAP3K1Low GBM (Figure A). Additionally, KEGG pathway analysis demonstrated multiple molecular pathways that were related to malignant cancer and therapeutic resistance, including cell cycle pathways and the NOTCH, DNA replication, and p53 pathways. Similar results were observed by gene set enrichment analysis (GSEA) (Figure C,D, and E).…”

Section: Resultsmentioning

confidence: 99%

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

et al. 2019

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Introduction Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long‐term outcome of glioma. Aims To further investigate prognostic biomarkers and potential therapeutic targets for GBM. Results In this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen‐activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy. Conclusion Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long‐term outcomes of GBM.

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BACH1 Promotes Temozolomide Resistance in Glioblastoma through Antagonizing the Function of p53

Cited by 30 publications

References 41 publications

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

Identification of WISP1 as a novel oncogene in glioblastoma

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

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