دورية أكاديمية
SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.
| العنوان: | SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression. |
|---|---|
| المؤلفون: | Shan L; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Wang W; College of Life Science, Northeast Forestry University, Harbin 150040, China., Du L; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Li D; College of Life Science, Northeast Forestry University, Harbin 150040, China., Wang Y; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Xie Y; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Li H; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Wang J; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Shi Z; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Zhou Y; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China., Zhu D; College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China., Sui G; College of Life Science, Northeast Forestry University, Harbin 150040, China., Liu F; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 16; Vol. 121 (29), pp. e2401834121. Date of Electronic Publication: 2024 Jul 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Sp1 Transcription Factor*/metabolism , Sp1 Transcription Factor*/genetics , Adenocarcinoma of Lung*/metabolism , Adenocarcinoma of Lung*/pathology , Adenocarcinoma of Lung*/genetics , Lung Neoplasms*/metabolism , Lung Neoplasms*/pathology , Lung Neoplasms*/genetics , RGS Proteins*/metabolism , RGS Proteins*/genetics , Gene Expression Regulation, Neoplastic*, Humans ; Cell Line, Tumor ; Animals ; Enhancer Elements, Genetic ; Disease Progression ; Mice ; Phase Separation |
| مستخلص: | Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation. Competing Interests: Competing interests statement:The authors declare no competing interest. |
| التعليقات: | Erratum in: Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2414313121. doi: 10.1073/pnas.2414313121. (PMID: 39102557) |
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| معلومات مُعتمدة: | 91339107 The Haiyan Foundation of Harbin Medical University Cancer Hospitalcancer h; NCC201908B11 The National Cancer Centre Climbing Foundation; 81270113 The Beijing Science and Technology Innovation Medical Development Foundation; 82273107 The National Natural Science Foundation of China |
| فهرسة مساهمة: | Keywords: RGS20; SP1; liquid–liquid phase separation; lung cancer; super-enhancer |
| المشرفين على المادة: | 0 (Sp1 Transcription Factor) 0 (RGS Proteins) 0 (SP1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240708 Date Completed: 20240708 Latest Revision: 20240805 |
| رمز التحديث: | 20240806 |
| مُعرف محوري في PubMed: | PMC11260144 |
| DOI: | 10.1073/pnas.2401834121 |
| PMID: | 38976739 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2401834121 |