دورية أكاديمية
Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.
| العنوان: | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma. |
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| المؤلفون: | Yin DP; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.; Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Soochow University, Suzhou, China., Zhang H; Department of Radiotherapy, Suzhou Ninth People's Hospital, Suzhou, China., Teng H; Department of Otorhinolaryngology Head and Neck Surgery, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China., Zhang D; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China., Chen P; Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Soochow University, Suzhou, China. chenpp1123@163.com., Xie L; Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Soochow University, Suzhou, China. xielixiaoxielixiao@163.com., Liu JS; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. sdfyyljs@sina.com. |
| المصدر: | Cell death & disease [Cell Death Dis] 2023 Dec 04; Vol. 14 (12), pp. 792. Date of Electronic Publication: 2023 Dec 04. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group |
| مواضيع طبية MeSH: | Nasopharyngeal Carcinoma*/genetics , Nasopharyngeal Carcinoma*/pathology , Nasopharyngeal Neoplasms*/genetics , Nasopharyngeal Neoplasms*/pathology , GTP-Binding Protein alpha Subunits, Gi-Go*/genetics , GTP-Binding Protein alpha Subunits, Gi-Go*/metabolism, Animals ; Humans ; Mice ; Cell Line, Tumor ; Cell Proliferation/genetics ; Mice, Nude ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Guide, CRISPR-Cas Systems ; RNA, Small Interfering/pharmacology ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Transcription Factors/pharmacology |
| مستخلص: | The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | 82002850 National Natural Science Foundation of China (National Science Foundation of China) |
| المشرفين على المادة: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (RNA, Guide, CRISPR-Cas Systems) 0 (RNA, Small Interfering) EC 2.7.11.1 (TOR Serine-Threonine Kinases) 0 (Transcription Factors) EC 3.6.5.1 (GNAI1 protein, human) EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go) |
| تواريخ الأحداث: | Date Created: 20231204 Date Completed: 20231206 Latest Revision: 20240403 |
| رمز التحديث: | 20240403 |
| مُعرف محوري في PubMed: | PMC10696052 |
| DOI: | 10.1038/s41419-023-06308-8 |
| PMID: | 38049415 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2041-4889 |
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| DOI: | 10.1038/s41419-023-06308-8 |