Cargando…
TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920937/ https://www.ncbi.nlm.nih.gov/pubmed/35279540 http://dx.doi.org/10.1016/j.tranon.2022.101391 |
_version_ | 1784669230443003904 |
---|---|
author | Cai, Jiayang Gao, Lun Wang, Yixuan Li, Yong Ye, Zhang Tong, Shiao Yan, Tengfeng sun, Qian Xu, Yang Jiang, Hongxiang Zhang, Si Zhao, Linyao Yang, Ji'an Chen, Qianxue |
author_facet | Cai, Jiayang Gao, Lun Wang, Yixuan Li, Yong Ye, Zhang Tong, Shiao Yan, Tengfeng sun, Qian Xu, Yang Jiang, Hongxiang Zhang, Si Zhao, Linyao Yang, Ji'an Chen, Qianxue |
author_sort | Cai, Jiayang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8920937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89209372022-03-21 TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway Cai, Jiayang Gao, Lun Wang, Yixuan Li, Yong Ye, Zhang Tong, Shiao Yan, Tengfeng sun, Qian Xu, Yang Jiang, Hongxiang Zhang, Si Zhao, Linyao Yang, Ji'an Chen, Qianxue Transl Oncol Original Research 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. Neoplasia Press 2022-03-10 /pmc/articles/PMC8920937/ /pubmed/35279540 http://dx.doi.org/10.1016/j.tranon.2022.101391 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Cai, Jiayang Gao, Lun Wang, Yixuan Li, Yong Ye, Zhang Tong, Shiao Yan, Tengfeng sun, Qian Xu, Yang Jiang, Hongxiang Zhang, Si Zhao, Linyao Yang, Ji'an Chen, Qianxue TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title | TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title_full | TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title_fullStr | TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title_full_unstemmed | TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title_short | TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway |
title_sort | tmbim1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 mapk signalling pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920937/ https://www.ncbi.nlm.nih.gov/pubmed/35279540 http://dx.doi.org/10.1016/j.tranon.2022.101391 |
work_keys_str_mv | AT caijiayang tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT gaolun tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT wangyixuan tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT liyong tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT yezhang tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT tongshiao tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT yantengfeng tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT sunqian tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT xuyang tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT jianghongxiang tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT zhangsi tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT zhaolinyao tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT yangjian tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway AT chenqianxue tmbim1promotesproliferationandattenuatesapoptosisinglioblastomacellsbytargetingthep38mapksignallingpathway |