Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting
Abstract Background Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significanc...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-020-1530-3 |
| _version_ | 1818388140312756224 |
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| author | Chaosheng Yu Fang Chen Xiaoqi Wang Zhimou Cai Mengxue Yang Qingwen Zhong Jialian Feng Junzheng Li Congxiang Shen Zhong Wen |
| author_facet | Chaosheng Yu Fang Chen Xiaoqi Wang Zhimou Cai Mengxue Yang Qingwen Zhong Jialian Feng Junzheng Li Congxiang Shen Zhong Wen |
| author_sort | Chaosheng Yu |
| collection | DOAJ |
| description | Abstract Background Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial–mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression. Methods Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs. Results We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs. Conclusions Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment. |
| first_indexed | 2024-12-14T04:21:06Z |
| format | Article |
| id | doaj.art-d42181fb6b064939bcac5b76ae7a9d1d |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-14T04:21:06Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-d42181fb6b064939bcac5b76ae7a9d1d2022-12-21T23:17:22ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-02-0139111310.1186/s13046-020-1530-3Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targetingChaosheng Yu0Fang Chen1Xiaoqi Wang2Zhimou Cai3Mengxue Yang4Qingwen Zhong5Jialian Feng6Junzheng Li7Congxiang Shen8Zhong Wen9Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical UniversityAbstract Background Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial–mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression. Methods Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs. Results We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs. Conclusions Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.https://doi.org/10.1186/s13046-020-1530-3PinX1Nasopharyngeal carcinomamiR-200bMigrationInvasionTranscriptional regulation |
| spellingShingle | Chaosheng Yu Fang Chen Xiaoqi Wang Zhimou Cai Mengxue Yang Qingwen Zhong Jialian Feng Junzheng Li Congxiang Shen Zhong Wen Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting Journal of Experimental & Clinical Cancer Research PinX1 Nasopharyngeal carcinoma miR-200b Migration Invasion Transcriptional regulation |
| title | Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting |
| title_full | Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting |
| title_fullStr | Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting |
| title_full_unstemmed | Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting |
| title_short | Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting |
| title_sort | pin2 telomeric repeat factor 1 interacting telomerase inhibitor 1 pinx1 inhibits nasopharyngeal cancer cell stemness implication for cancer progression and therapeutic targeting |
| topic | PinX1 Nasopharyngeal carcinoma miR-200b Migration Invasion Transcriptional regulation |
| url | https://doi.org/10.1186/s13046-020-1530-3 |
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