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.
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TMBIM 1通过靶向p38 MAPK信号通路促进胶质母细胞瘤细胞增殖并减弱凋亡。
DOI：
10.1016/j.tranon.2022.101391
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发表时间：
2022-05
影响因子：
5
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Cai J;Gao L;Wang Y;Li Y;Ye Z;Tong S;Yan T;Sun Q;Xu Y;Jiang H;Zhang S;Zhao L;Yang J;Chen Q
我们的研究首次发现TMBIM1在GBM中通过p38/MAPK通路促进增殖和减弱凋亡。我们还发现TMBIM1调节GBM细胞对TMZ的敏感性。我们的研究将为今后GBM分子机制的深入研究提供重要依据，TMBIM1可能是治疗GBM的潜在靶点。多形性胶质母细胞瘤（GBM）是成人最常见和最致命的原发性恶性脑肿瘤。患者确诊后的平均生存时间仅为12-15个月。其过度增殖和逃避细胞凋亡的特点对患者预后不良起着至关重要的作用。因此，研究GBM的分子机制，寻找有效的治疗靶点来克服这一困境是值得的。在本研究中，含有1的跨膜BAX抑制剂motif （TMBIM1）在GBM组织中高表达，TMBIM1在GBM细胞系（U87和U251）中高表达可促进细胞增殖，抑制细胞周期阻滞。此外，TMBIM1能显著减缓GBM细胞凋亡，降低GBM细胞对替莫唑胺（TMZ）的敏感性。在分子机制方面，我们发现TMBIM1通过抑制p38磷酸化，干扰p38/MAPK通路，促进细胞增殖，减轻细胞凋亡。体内实验表明，TMBIM1敲低组小鼠的存活时间明显延长。这一发现为今后GBM分子机制的深入研究提供了重要基础，并为GBM的治疗提供了潜在的靶点。
Our research firstly identified that TMBIM1 promotes proliferation and attenuates apoptosis via the p38/MAPK pathway in GBM. We also revealed that TMBIM1 regulates the sensitivity of GBM cells to TMZ. Our research will provide an important basis for future intensive molecular mechanism research in GBM and TMBIM1 might be a potential therapeutic target for treating GBM. 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.
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影响因子：
4
作者：
Arnau-Collell C;Soares de Lima Y;Díaz-Gay M;Muñoz J;Carballal S;Bonjoch L;Moreira L;Lozano JJ;Ocaña T;Cuatrecasas M;Díaz de Bustamante A;Castells A;Capellà G;Bujanda L;Cubiella J;Rodríguez-Alcalde D;Balaguer F;Ruiz-Ponte C;Valle L;Moreno V;Castellvi-Bel S
通讯作者：
Castellvi-Bel S
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
30.8
作者：
Hui, Lijian;Bakiri, Latifa;Wagner, Erwin F.
通讯作者：
Wagner, Erwin F.
影响因子：
7.2
作者：
Hu, Lan;Smith, Temple F.;Goldberger, Gabriel
通讯作者：
Goldberger, Gabriel
影响因子：
3.8
作者：
Jang SH;Kim AR;Park NH;Park JW;Han IS
通讯作者：
Han IS