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In vivo genome-wide CRISPR screening identifies ZNF24 as a negative NF-κB modulator in lung cancer

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机构： [1]MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China [2]Department of Chemistry, Jinan University, Guangzhou 510632, China [3]Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

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关键词： Lung cancer Tumor suppressor gene ZNF24 NF-κB Combination therapy

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Systemic identification of tumor suppressor genes (TSGs) and elucidation of their signaling provide a new angle for understanding of tumorigenesis, which is important for developing successful treatment for lung cancer patients. In our current work, we conducted an in vivo screen for lung cancer TSGs through CRISPR/Cas9 mediated knockout of genes at genome-wide scale. We found that ZNF24 was a potent and clinically relevant TSG of lung cancer. Ectopic expression of ZNF24 arrested lung cancer cells in S phase. Mechanistically, ZNF24 bound to promoter region of P65 to negatively regulate its transcription and thereby the signaling activity of NF-κB pathway. This signaling cascade is clinically relevant. Importantly, we found that combinational inhibition of KRAS, NF-κB, and PD-1 effectively shrank autochthonous KrasG12D/ZNF24-/- lung cancers in transgenic mouse model. Our current work thus revealed an important role played by loss of function of ZNF24 in lung tumorigenesis and shed new light in precision medicine for a portion of lung cancer patients.© 2022. The Author(s).

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出版当年[2021]版：

大类 | 3 区生物学

小类 | 3 区生化与分子生物学

最新[2025]版：

大类 | 2 区

生物学

小类 | 2 区生化与分子生物学

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出版当年[2020]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

最新[2023]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 6.1 最新[2023版] 7 最新五年平均 7.133 出版当年[2020版] 6.302 出版当年五年平均 5.026 出版前一年[2019版] 9.597 出版后一年[2021版]

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第一作者机构： [1]MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China

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