Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer
Abstract Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with limited treatment options and poor prognosis in advanced stages. Arsenic trioxide (ATO), a drug well-known for treating acute promyelocytic leukemia, has shown potential antitumor effects in several solid tumors. This study...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-12881-z |
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| author | Yanru Ren Xiao Yang Yang Hui Weiyao Chen Yi Cheng Ning Zhang Tao Liu Xinxin Yang Xiaoyu Li |
| author_facet | Yanru Ren Xiao Yang Yang Hui Weiyao Chen Yi Cheng Ning Zhang Tao Liu Xinxin Yang Xiaoyu Li |
| author_sort | Yanru Ren |
| collection | DOAJ |
| description | Abstract Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with limited treatment options and poor prognosis in advanced stages. Arsenic trioxide (ATO), a drug well-known for treating acute promyelocytic leukemia, has shown potential antitumor effects in several solid tumors. This study aimed to investigate the role of ATO on LSCC proliferation and its underlying molecular mechanisms. LSCC cell lines (TU212, TU686, and AMC-HN-8) were treated with varying concentrations of ATO, and cell proliferation was evaluated using CCK-8, colony formation, and EdU assays. miRNA-sequencing identified differentially expressed miRNAs after ATO treatment, and bioinformatics tools predicted hsa-miR-573 target genes. The interaction between hsa-miR-573 and dynactin-associated protein (DYNAP) was validated by dual-luciferase reporter assays. Additionally, a xenograft tumor model was established to examine the in vivo effects of ATO on tumor growth. ATO significantly inhibited LSCC cell proliferation in a dose- and time-dependent manner. miRNA-sequencing identified hsa-miR-573 as significantly upregulated following ATO treatment, and functional studies demonstrated that hsa-miR-573 suppresses LSCC cell proliferation by directly targeting DYNAP. Overexpression of DYNAP promoted LSCC cell proliferation, while DYNAP knockdown reversed this effect. In vivo, ATO treatment suppressed tumor growth in nude mice without significant nephrotoxicity or cardiotoxicity. Mechanistically, ATO reduced the expression of DYNAP and inhibited the PI3K/AKT signaling pathway. ATO inhibited LSCC progression by upregulating hsa-miR-573, which directly targets DYNAP to suppress cell proliferation and disrupt the PI3K/AKT signaling pathway. These findings supported the potential of ATO as a therapeutic agent for LSCC. |
| format | Article |
| id | doaj-art-9d1e4bb5a1144ad3b2c596c26bb67787 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-9d1e4bb5a1144ad3b2c596c26bb677872025-08-20T04:03:02ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-12881-zArsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancerYanru Ren0Xiao Yang1Yang Hui2Weiyao Chen3Yi Cheng4Ning Zhang5Tao Liu6Xinxin Yang7Xiaoyu Li8School of Clinical Medicine, Jining Medical UniversityDepartment of Stomatology, Affiliated Hospital of Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversitySchool of Clinical Medicine, Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Jining Medical UniversityAbstract Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with limited treatment options and poor prognosis in advanced stages. Arsenic trioxide (ATO), a drug well-known for treating acute promyelocytic leukemia, has shown potential antitumor effects in several solid tumors. This study aimed to investigate the role of ATO on LSCC proliferation and its underlying molecular mechanisms. LSCC cell lines (TU212, TU686, and AMC-HN-8) were treated with varying concentrations of ATO, and cell proliferation was evaluated using CCK-8, colony formation, and EdU assays. miRNA-sequencing identified differentially expressed miRNAs after ATO treatment, and bioinformatics tools predicted hsa-miR-573 target genes. The interaction between hsa-miR-573 and dynactin-associated protein (DYNAP) was validated by dual-luciferase reporter assays. Additionally, a xenograft tumor model was established to examine the in vivo effects of ATO on tumor growth. ATO significantly inhibited LSCC cell proliferation in a dose- and time-dependent manner. miRNA-sequencing identified hsa-miR-573 as significantly upregulated following ATO treatment, and functional studies demonstrated that hsa-miR-573 suppresses LSCC cell proliferation by directly targeting DYNAP. Overexpression of DYNAP promoted LSCC cell proliferation, while DYNAP knockdown reversed this effect. In vivo, ATO treatment suppressed tumor growth in nude mice without significant nephrotoxicity or cardiotoxicity. Mechanistically, ATO reduced the expression of DYNAP and inhibited the PI3K/AKT signaling pathway. ATO inhibited LSCC progression by upregulating hsa-miR-573, which directly targets DYNAP to suppress cell proliferation and disrupt the PI3K/AKT signaling pathway. These findings supported the potential of ATO as a therapeutic agent for LSCC.https://doi.org/10.1038/s41598-025-12881-zLaryngeal cancerProliferative capacityArsenic trioxideHsa-mir-573Dynactin-associated proteinPI3K/AKT pathway |
| spellingShingle | Yanru Ren Xiao Yang Yang Hui Weiyao Chen Yi Cheng Ning Zhang Tao Liu Xinxin Yang Xiaoyu Li Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer Scientific Reports Laryngeal cancer Proliferative capacity Arsenic trioxide Hsa-mir-573 Dynactin-associated protein PI3K/AKT pathway |
| title | Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer |
| title_full | Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer |
| title_fullStr | Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer |
| title_full_unstemmed | Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer |
| title_short | Arsenic trioxide regulates DYNAP through hsa-mir-573 and inhibits the proliferation of laryngeal cancer |
| title_sort | arsenic trioxide regulates dynap through hsa mir 573 and inhibits the proliferation of laryngeal cancer |
| topic | Laryngeal cancer Proliferative capacity Arsenic trioxide Hsa-mir-573 Dynactin-associated protein PI3K/AKT pathway |
| url | https://doi.org/10.1038/s41598-025-12881-z |
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