ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells
ING5 belongs to the inhibitor of growth (ING) candidate tumor suppressor family, which is involved in multiple cellular functions, such as cell cycle regulation, apoptosis, and chromatin remodelling. Previously, we reported that ING5 overexpression inhibits EMT by regulating EMT-related molecules, i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023074 |
| _version_ | 1797635803583610880 |
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| author | Yang Jiong Liu Xinli Sun Yang Zhang Xutao Zhao Yong Zhang Haihua Mei Qibing Meng Jin Zhang Feng Zhang Tao |
| author_facet | Yang Jiong Liu Xinli Sun Yang Zhang Xutao Zhao Yong Zhang Haihua Mei Qibing Meng Jin Zhang Feng Zhang Tao |
| author_sort | Yang Jiong |
| collection | DOAJ |
| description | ING5 belongs to the inhibitor of growth (ING) candidate tumor suppressor family, which is involved in multiple cellular functions, such as cell cycle regulation, apoptosis, and chromatin remodelling. Previously, we reported that ING5 overexpression inhibits EMT by regulating EMT-related molecules, including Snail1, at the mRNA and protein levels. However, the mechanisms remain unclear. In the current study, we identify that ING5 overexpression induces the upregulation of miR-34c-5p. The expression levels of both ING5 and miR-34c-5p in NSCLC tissues from the TCGA database are decreased compared with that in adjacent tissues. Higher expression levels of both ING5 and miR-34c-5p predict longer overall survival (OS). Snail1 is the target gene of miR-34c-5p, as predicted by an online database, which is further verified by a dual-luciferase reporter assay. The expression level of Snail1 in NSCLC cells is markedly reduced following miR-34c-5p overexpression, leading to the inactivation of the Snail1 downstream TGF-β/Smad3 signaling pathway. The TGF-β signaling-specific inhibitor LY2157299 reverses the enhanced EMT, proliferation, migration, and invasion abilities induced by the miR-34c-5p inhibitor. Furthermore, tail vein injection of miR-34c-5p agomir inhibits xenografted tumor metastasis. Overall, this study concludes that miR-34c-5p, induced by ING5 overexpression, is a tumor suppressor that targets Snail1 and mediates the inhibitory effects of ING5 on the EMT and invasion of NSCLC cells. These results provide a novel mechanism mediating the antitumor effects of ING5. |
| first_indexed | 2024-03-11T12:26:33Z |
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| id | doaj.art-4240965a771d4b1c927ca1e5e5de45db |
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| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:33Z |
| publishDate | 2023-05-01 |
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| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-4240965a771d4b1c927ca1e5e5de45db2023-11-06T08:47:36ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-05-015580981710.3724/abbs.202307420d259ccING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cellsYang Jiong0Liu Xinli1Sun Yang2Zhang Xutao3Zhao Yong4Zhang Haihua5Mei Qibing6Meng Jin7Zhang Feng8Zhang Tao9["Medical Supplies Center of PLA General Hospital, Beijing 100853, China"]["Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi’an 710032, China"]["Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi’an 710032, China"]["Department of Clinical Aerospace Medicine, Air force Medical University, Xi’an 710032, China"]["Laboratory Animal Center, Air Force Medical University, Xi’an 710032, China"]["Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China"]["Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi’an 710032, China"]["Medical Supplies Center of PLA General Hospital, Beijing 100853, China"]["Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi’an 710032, China"]["Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China"]ING5 belongs to the inhibitor of growth (ING) candidate tumor suppressor family, which is involved in multiple cellular functions, such as cell cycle regulation, apoptosis, and chromatin remodelling. Previously, we reported that ING5 overexpression inhibits EMT by regulating EMT-related molecules, including Snail1, at the mRNA and protein levels. However, the mechanisms remain unclear. In the current study, we identify that ING5 overexpression induces the upregulation of miR-34c-5p. The expression levels of both ING5 and miR-34c-5p in NSCLC tissues from the TCGA database are decreased compared with that in adjacent tissues. Higher expression levels of both ING5 and miR-34c-5p predict longer overall survival (OS). Snail1 is the target gene of miR-34c-5p, as predicted by an online database, which is further verified by a dual-luciferase reporter assay. The expression level of Snail1 in NSCLC cells is markedly reduced following miR-34c-5p overexpression, leading to the inactivation of the Snail1 downstream TGF-β/Smad3 signaling pathway. The TGF-β signaling-specific inhibitor LY2157299 reverses the enhanced EMT, proliferation, migration, and invasion abilities induced by the miR-34c-5p inhibitor. Furthermore, tail vein injection of miR-34c-5p agomir inhibits xenografted tumor metastasis. Overall, this study concludes that miR-34c-5p, induced by ING5 overexpression, is a tumor suppressor that targets Snail1 and mediates the inhibitory effects of ING5 on the EMT and invasion of NSCLC cells. These results provide a novel mechanism mediating the antitumor effects of ING5.https://www.sciengine.com/doi/10.3724/abbs.2023074inhibitor of growth protein 5 (ING5), miR-34c-5pnon-small cell lung cancer (NSCLC), invasion and metastasis, diagnostic and prognostic biomarkers |
| spellingShingle | Yang Jiong Liu Xinli Sun Yang Zhang Xutao Zhao Yong Zhang Haihua Mei Qibing Meng Jin Zhang Feng Zhang Tao ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells Acta Biochimica et Biophysica Sinica inhibitor of growth protein 5 (ING5), miR-34c-5p non-small cell lung cancer (NSCLC), invasion and metastasis, diagnostic and prognostic biomarkers |
| title | ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells |
| title_full | ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells |
| title_fullStr | ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells |
| title_full_unstemmed | ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells |
| title_short | ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells |
| title_sort | ing5 overexpression upregulates mir 34c 5p snail1 to inhibit emt and invasion of lung cancer cells |
| topic | inhibitor of growth protein 5 (ING5), miR-34c-5p non-small cell lung cancer (NSCLC), invasion and metastasis, diagnostic and prognostic biomarkers |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023074 |
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