HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma
Abstract Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the pres...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04538-0 |
| _version_ | 1797556888520359936 |
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| author | Yong Zhong Fan Yu Ling Yang Yu Wang Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Shiyang Sheng Zhongwei Lv Li Weng Bo Wu Xiaoping Zhang |
| author_facet | Yong Zhong Fan Yu Ling Yang Yu Wang Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Shiyang Sheng Zhongwei Lv Li Weng Bo Wu Xiaoping Zhang |
| author_sort | Yong Zhong |
| collection | DOAJ |
| description | Abstract Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial–mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3′-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC. Graphical Abstract |
| first_indexed | 2024-03-10T17:09:26Z |
| format | Article |
| id | doaj.art-e9d7c4a5f8c548efa72469976c6585bd |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-10T17:09:26Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-e9d7c4a5f8c548efa72469976c6585bd2023-11-20T10:44:06ZengBMCJournal of Translational Medicine1479-58762023-11-0121112310.1186/s12967-023-04538-0HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinomaYong Zhong0Fan Yu1Ling Yang2Yu Wang3Lin Liu4Chengyou Jia5Haidong Cai6Jianshe Yang7Shiyang Sheng8Zhongwei Lv9Li Weng10Bo Wu11Xiaoping Zhang12Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of General Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer CenterDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Intervention, Tongren Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityAbstract Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial–mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3′-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC. Graphical Abstracthttps://doi.org/10.1186/s12967-023-04538-0Anaplastic thyroid carcinomaHOXD9miR-451aPSMB8MetastasisProliferation |
| spellingShingle | Yong Zhong Fan Yu Ling Yang Yu Wang Lin Liu Chengyou Jia Haidong Cai Jianshe Yang Shiyang Sheng Zhongwei Lv Li Weng Bo Wu Xiaoping Zhang HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma Journal of Translational Medicine Anaplastic thyroid carcinoma HOXD9 miR-451a PSMB8 Metastasis Proliferation |
| title | HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma |
| title_full | HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma |
| title_fullStr | HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma |
| title_full_unstemmed | HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma |
| title_short | HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma |
| title_sort | hoxd9 mir 451a psmb8 axis is implicated in the regulation of cell proliferation and metastasis via pi3k akt signaling pathway in human anaplastic thyroid carcinoma |
| topic | Anaplastic thyroid carcinoma HOXD9 miR-451a PSMB8 Metastasis Proliferation |
| url | https://doi.org/10.1186/s12967-023-04538-0 |
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