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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Main Authors: Song Chen, Xue Luo, Wentai Wang, Xing-hong Chen, Ning Ma, Xue-yin Zhu, Tian Zhou, Qing-jun Gao, Dai-wei Zhao
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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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
collection DOAJ
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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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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