Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma
Abstract 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 o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06308-8 |
| _version_ | 1797397771312955392 |
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| author | De-Pei Yin Huanle Zhang Hua Teng Dan Zhang Peipei Chen Lixiao Xie Ji-Sheng Liu |
| author_facet | De-Pei Yin Huanle Zhang Hua Teng Dan Zhang Peipei Chen Lixiao Xie Ji-Sheng Liu |
| author_sort | De-Pei Yin |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T01:14:58Z |
| format | Article |
| id | doaj.art-bc4d482ceb0a4f3dbc5240511e81c37d |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-09T01:14:58Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-bc4d482ceb0a4f3dbc5240511e81c37d2023-12-10T12:33:31ZengNature Publishing GroupCell Death and Disease2041-48892023-12-01141211310.1038/s41419-023-06308-8Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinomaDe-Pei Yin0Huanle Zhang1Hua Teng2Dan Zhang3Peipei Chen4Lixiao Xie5Ji-Sheng Liu6Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Radiotherapy, Suzhou Ninth People’s HospitalDepartment of Otorhinolaryngology Head and Neck Surgery, Jiangsu Province Hospital on Integration of Chinese and Western MedicineDepartment of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Children’s Hospital of Soochow UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Children’s Hospital of Soochow UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Soochow UniversityAbstract 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.https://doi.org/10.1038/s41419-023-06308-8 |
| spellingShingle | De-Pei Yin Huanle Zhang Hua Teng Dan Zhang Peipei Chen Lixiao Xie Ji-Sheng Liu Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma Cell Death and Disease |
| title | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma |
| title_full | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma |
| title_fullStr | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma |
| title_full_unstemmed | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma |
| title_short | Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma |
| title_sort | overexpressed gαi1 exerts pro tumorigenic activity in nasopharyngeal carcinoma |
| url | https://doi.org/10.1038/s41419-023-06308-8 |
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