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| Format: | Artículo científico |
| Sprache: | en |
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BMC biology
2026
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| Online-Zugang: | https://pubmed.ncbi.nlm.nih.gov/41546036/ |
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| author | Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao |
| author_facet | Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao |
| collection | PubMed - marine biology |
| contents | BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53. Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao Humans Bromodomain Containing Proteins Adenocarcinoma of Lung Transcription Factors Lung Neoplasms LIM Domain Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Tumor Suppressor Protein p53 Animals Transcriptional Activation Cell Line, Tumor Mice Gene Expression Regulation, Neoplastic Understanding p53-independent regulatory mechanisms is crucial for predicting outcomes in lung adenocarcinoma (LUAD) and developing improved therapeutic strategies. We found that PDLIM4 is highly expressed in LUAD tumor tissues, where it induces G2/M phase cell cycle arrest and suppresses cell proliferation, suggesting its potential role in improving patient prognosis. Our study identified BRD4, a bromodomain and extraterminal (BET) family protein, as a key transcriptional regulator of PDLIM4, acting through its BD1 domain. Further analysis revealed that wild-type PDLIM4 stabilizes p21 by blocking its RNA degradation, leading to p21 protein accumulation and subsequent inhibition of cell proliferation. In contrast, the S116 mutation in PDLIM4 abrogates this regulatory effect. Notably, activation of the BRD4/PDLIM4/p21 pathway enhanced chemosensitivity to doxorubicin in both LUAD cells and xenograft tumor models. Given the high mutation frequency of PDLIM4 recorded in the TCGA cancer database, our findings reveal a critical regulatory signaling pathway that suppresses LUAD progression and augments chemotherapy efficacy. |
| format | Artículo científico |
| id | pubmed_41546036 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | BMC biology |
| record_format | pubmed |
| spellingShingle | BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53. Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao Humans Bromodomain Containing Proteins Adenocarcinoma of Lung Transcription Factors Lung Neoplasms LIM Domain Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Tumor Suppressor Protein p53 Animals Transcriptional Activation Cell Line, Tumor Mice Gene Expression Regulation, Neoplastic BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53. Wang, Qingwei Guo, Liangsheng Wang, Shuai Guan, Chengdan Pan, Junhao Zhu, Shaoping Zheng, Lei Wu, Xuehua Gu, Yonghui Shu, Tao Luo, Lianxiang Lai, Tianwen Gao, Xiao Humans Bromodomain Containing Proteins Adenocarcinoma of Lung Transcription Factors Lung Neoplasms LIM Domain Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Tumor Suppressor Protein p53 Animals Transcriptional Activation Cell Line, Tumor Mice Gene Expression Regulation, Neoplastic Understanding p53-independent regulatory mechanisms is crucial for predicting outcomes in lung adenocarcinoma (LUAD) and developing improved therapeutic strategies. We found that PDLIM4 is highly expressed in LUAD tumor tissues, where it induces G2/M phase cell cycle arrest and suppresses cell proliferation, suggesting its potential role in improving patient prognosis. Our study identified BRD4, a bromodomain and extraterminal (BET) family protein, as a key transcriptional regulator of PDLIM4, acting through its BD1 domain. Further analysis revealed that wild-type PDLIM4 stabilizes p21 by blocking its RNA degradation, leading to p21 protein accumulation and subsequent inhibition of cell proliferation. In contrast, the S116 mutation in PDLIM4 abrogates this regulatory effect. Notably, activation of the BRD4/PDLIM4/p21 pathway enhanced chemosensitivity to doxorubicin in both LUAD cells and xenograft tumor models. Given the high mutation frequency of PDLIM4 recorded in the TCGA cancer database, our findings reveal a critical regulatory signaling pathway that suppresses LUAD progression and augments chemotherapy efficacy. |
| title | BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53. |
| topic | Humans Bromodomain Containing Proteins Adenocarcinoma of Lung Transcription Factors Lung Neoplasms LIM Domain Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Tumor Suppressor Protein p53 Animals Transcriptional Activation Cell Line, Tumor Mice Gene Expression Regulation, Neoplastic |
| url | https://pubmed.ncbi.nlm.nih.gov/41546036/ |