2. Academic Validation
  3. TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway

TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway

  • Transl Oncol. 2022 May;19:101391. doi: 10.1016/j.tranon.2022.101391.
Jiayang Cai 1,  Lun Gao 2,  Yixuan Wang 3,  Yong Li 4,  Zhang Ye 5,  Shiao Tong 6,  Tengfeng Yan 7,  Qian Sun 8,  Yang Xu 9,  Hongxiang Jiang 10,  Si Zhang 11,  Linyao Zhao 12,  Ji'an Yang 13,  Qianxue Chen 14
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: jiaycai@whu.edu.cn.
  • 2 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: lungao@whu.edu.cn.
  • 3 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: wang666@whu.edu.cn.
  • 4 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: liyong12358@sina.com.
  • 5 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: yezhang@whu.edu.cn.
  • 6 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: tongshiao@whu.edu.cn.
  • 7 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: 2019103020026@whu.edu.cn.
  • 8 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: sunqian666@whu.edu.cn.
  • 9 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: xuyang0909@whu.edu.cn.
  • 10 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: HX-jiang@whu.edu.cn.
  • 11 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: 2015302180314@whu.edu.cn.
  • 12 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: linyao_zh@whu.edu.cn.
  • 13 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: jayang@whu.edu.cn.
  • 14 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. Electronic address: chenqx666@whu.edu.cn.
PMID: 35279540 DOI: 10.1016/j.tranon.2022.101391
Abstract

Glioblastoma multiforme (GBM) is the most common and most fatal primary malignant brain tumour in adults. The average survival time of patients after diagnosis is only 12-15 months. And its characteristics of excessive proliferation and Apoptosis evasion play a crucial role in the poor prognosis of patients. Therefore, it is worth investigating the molecular mechanism of GBM to find an effective therapeutic target to overcome the dilemma. In the current study, Transmembrane Bax Inhibitor motif containing 1 (TMBIM1) was highly expressed in GBM tissues and high TMBIM1 expression in GBM cell lines (U87 and U251) could promote cell proliferation and inhibit cell cycle arrest. In addition, TMBIM1 could significantly attenuate GBM cell Apoptosis and decrease the sensitivity of GBM cells to temozolomide (TMZ). In terms of the molecular mechanism, we revealed that TMBIM1 interferes with the p38/MAPK pathway by inhibiting p38 phosphorylation to promote cell proliferation and attenuate cell Apoptosis. In vivo experiments showed that the survival time of mice in TMBIM1 knockdown group was significantly prolonged. Our discovery provided an important basis for future intensive molecular mechanism research in GBM and presented a potential target for the treatment of GBM.

Keywords

Apoptosis; Glioblastoma; Proliferation; TMBIM1; p38 MAPK.

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