title: TAZ promotes temozolomide resistance by upregulating MCL-1 in human glioma cells.
abstract: Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). However, intrinsic or acquired chemoresistance to temozolomide remains the greatest obstacle to the successful treatment of human GBM. The principal mechanism responsible for this resistance is largely unknown. In the present study, we showed that expression of transcriptional co-activator with PDZ-binding motif (TAZ) in glioma cells correlated with temozolomide chemoresistance in human glioma cells. Overexpression of TAZ promoted temozolomide resistance in U-87MG cells, whereas knockdown of TAZ expression sensitized temozolomide-resistant U-251MG cells to temozolomide. Further, TAZ inhibits temozolomide induced apoptosis via upregulation of MCL-1 (myeloid cell leukemia 1) and high expression of TAZ predicts a poor prognosis for GBM patients. In conclusion, our results suggest that TAZ had a critical role in the resistance to temozolomide in glioma cells, and it may provide a promising target for improving the therapeutic outcome of temozolomide-resistant gliomas.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China; Institute of Clinical Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: tiantian_2016@126.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China; Institute of Clinical Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Yichang Central People's Hospital and the First Affiliated Hospital of China Three Gorges University, 443002, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China; Institute of Clinical Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: zhaomingli2013@163.com.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Li
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D011379:Prognosis; D000077204:Temozolomide; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D047908:Intracellular Signaling Peptides and Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Apoptosis; Glioma; TAZ; Temozolomide resistance