ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration
Abstract Alpha-actin-1 (ACTN1) is a cytoskeletal protein, and new evidence suggests that it is associated with tumor progression and prognosis. However, the expression of ACTN1 in thyroid carcinoma (THCA) and its biological functions are not fully understood. This study aimed to explore the expressi...
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2024-12-01
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Online Access: | https://doi.org/10.1038/s41598-024-83719-3 |
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author | Song Chen Xue Luo Wentai Wang Xing-hong Chen Ning Ma Xue-yin Zhu Tian Zhou Qing-jun Gao Dai-wei Zhao |
author_facet | Song Chen Xue Luo Wentai Wang Xing-hong Chen Ning Ma Xue-yin Zhu Tian Zhou Qing-jun Gao Dai-wei Zhao |
author_sort | Song Chen |
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description | Abstract Alpha-actin-1 (ACTN1) is a cytoskeletal protein, and new evidence suggests that it is associated with tumor progression and prognosis. However, the expression of ACTN1 in thyroid carcinoma (THCA) and its biological functions are not fully understood. This study aimed to explore the expression and biological function of ACTN1 in THCA. Bioinformatics analysis revealed that ACTN1 was significantly upregulated in THCA and was associated with tumor size, extraglandular invasion, lymph node and distant metastasis, patient prognosis, and immune cell infiltration. qRT-PCR, immunohistochemistry, and western blotting verified the high expression of ACTN1 in the PTC samples. In vitro and in vivo experiments showed that overexpression of ACTN1 promoted THCA cell proliferation, cell cycle, migration, and invasion, and induced epithelial-mesenchymal transition (EMT); knockdown of ACTN1 inhibited these malignant behaviors. Mechanistically, ACTN1 knockdown reduced the phosphorylation levels of PI3K, AKT, and mTOR, whereas its overexpression increased these levels. After treating ACTN1 knockdown cells with the PI3K activator 740Y-P, the invasion and migration ability of the tumor was restored, suggesting that ACTN1 may promote the invasion and migration of THCA by activating the PI3K/AKT/mTOR pathway. In conclusion, ACTN1 is an important regulator of THCA progression and may serve as a potential molecular marker for predicting THCA invasion and metastasis. |
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institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2024-12-01 |
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spelling | doaj-art-d3f4cdfe61c645f7ade7e7365f74611b2025-01-05T12:24:38ZengNature PortfolioScientific Reports2045-23222024-12-0114111910.1038/s41598-024-83719-3ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltrationSong Chen0Xue Luo1Wentai Wang2Xing-hong Chen3Ning Ma4Xue-yin Zhu5Tian Zhou6Qing-jun Gao7Dai-wei Zhao8School of Clinical Medicine, GuiZhou Medical UniversityDepartment of Thyroid Surgery, Affiliated Hospital of Guizhou Medical UniversityThe Affiliated Stomatological Hospital of Guizhou Medical UniversityDepartment of Thyroid and Breast Surgery, Second People’s Hospital of Guizhou ProvinceSchool of Clinical Medicine, GuiZhou Medical UniversitySchool of Clinical Medicine, GuiZhou Medical UniversitySchool of Clinical Medicine, GuiZhou Medical UniversityDepartment of Thyroid Surgery, Affiliated Hospital of Guizhou Medical UniversitySchool of Clinical Medicine, GuiZhou Medical UniversityAbstract Alpha-actin-1 (ACTN1) is a cytoskeletal protein, and new evidence suggests that it is associated with tumor progression and prognosis. However, the expression of ACTN1 in thyroid carcinoma (THCA) and its biological functions are not fully understood. This study aimed to explore the expression and biological function of ACTN1 in THCA. Bioinformatics analysis revealed that ACTN1 was significantly upregulated in THCA and was associated with tumor size, extraglandular invasion, lymph node and distant metastasis, patient prognosis, and immune cell infiltration. qRT-PCR, immunohistochemistry, and western blotting verified the high expression of ACTN1 in the PTC samples. In vitro and in vivo experiments showed that overexpression of ACTN1 promoted THCA cell proliferation, cell cycle, migration, and invasion, and induced epithelial-mesenchymal transition (EMT); knockdown of ACTN1 inhibited these malignant behaviors. Mechanistically, ACTN1 knockdown reduced the phosphorylation levels of PI3K, AKT, and mTOR, whereas its overexpression increased these levels. After treating ACTN1 knockdown cells with the PI3K activator 740Y-P, the invasion and migration ability of the tumor was restored, suggesting that ACTN1 may promote the invasion and migration of THCA by activating the PI3K/AKT/mTOR pathway. In conclusion, ACTN1 is an important regulator of THCA progression and may serve as a potential molecular marker for predicting THCA invasion and metastasis.https://doi.org/10.1038/s41598-024-83719-3Thyroid cancerACTN1Tumour immunityEpithelial‒mesenchymal transition (EMT)Tumour metastasisAggressive subtypes |
spellingShingle | Song Chen Xue Luo Wentai Wang Xing-hong Chen Ning Ma Xue-yin Zhu Tian Zhou Qing-jun Gao Dai-wei Zhao ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration Scientific Reports Thyroid cancer ACTN1 Tumour immunity Epithelial‒mesenchymal transition (EMT) Tumour metastasis Aggressive subtypes |
title | ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration |
title_full | ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration |
title_fullStr | ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration |
title_full_unstemmed | ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration |
title_short | ACTN1 promotes cell invasion, migration, and EMT in thyroid cancer and is associated with immune infiltration |
title_sort | actn1 promotes cell invasion migration and emt in thyroid cancer and is associated with immune infiltration |
topic | Thyroid cancer ACTN1 Tumour immunity Epithelial‒mesenchymal transition (EMT) Tumour metastasis Aggressive subtypes |
url | https://doi.org/10.1038/s41598-024-83719-3 |
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