Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin
There are three isoforms of human collagen prolyl 4-hydroxylases (C-P4Hs), each of which has been reported to play an important role in regulating the progression of a variety of human cancers. By analyzing TGCA datasets on human head and n...
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China Science Publishing & Media Ltd.
2024-10-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024140 |
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| author | Xu Miao Shi Run Yang Jie Chen Heng Liu Shihua Yu Shupei Li Sasa He Wenqiang Sy Man-Sun Lu Mingjian Zhang Huixia Li Chaoyang |
| author_facet | Xu Miao Shi Run Yang Jie Chen Heng Liu Shihua Yu Shupei Li Sasa He Wenqiang Sy Man-Sun Lu Mingjian Zhang Huixia Li Chaoyang |
| author_sort | Xu Miao |
| collection | DOAJ |
| description | There are three isoforms of human collagen prolyl 4-hydroxylases (C-P4Hs), each of which has been reported to play an important role in regulating the progression of a variety of human cancers. By analyzing TGCA datasets on human head and neck squamous cell carcinoma (HNSC), we find that a higher expression of all three C-P4HAs (the <sc>α subunit</sc> of C-P4Hs) is a superior prognostic indicator than a higher expression of two or a single C-P4HA. Unexpectedly, some patients with higher levels of three C-P4HAs survive longer than patients whose tumors have lower expression of C-P4HAs. Therefore, there may be molecule(s) that can negate the deleterious effects of overexpressing C-P4HAs during cancer progression. By constructing a functional protein interaction network of <sc>C-P4HAs</sc> and analyzing molecules whose expressions are correlated significantly with that of C-P4HAs, we identify scribble cell polarity complex component 2 (LLGL2) as a factor that antagonizes the effects of overexpressed <sc>C-P4HAs</sc> on HNSC. Silencing of LLGL2 in the human oral squamous cell line Cal-27 upregulates the expression of occludin and increases cancer cell invasion and migration. In contrast, knocking down C-P4HA alone inhibits cell migration and invasion. Furthermore, simultaneously downregulating three C-P4HAs has more pronounced effects on inhibiting cell migration and invasion. Accordingly, high LLGL2 expression is also a marker indicating improved prognosis in patients with HNSC. These results suggest that the interplay between LLGL2 and C-P4HAs may be targeted to mitigate HNSC tumorigenesis and progression. <?Pub Caret 31?> |
| format | Article |
| id | doaj-art-a4bc8ca054934b22b48b170907f8ec32 |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-a4bc8ca054934b22b48b170907f8ec322025-01-17T05:58:32ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-10-01561833184710.3724/abbs.202414020d259ccCollagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludinXu Miao0Shi Run1Yang Jie2Chen Heng3Liu Shihua4Yu Shupei5Li Sasa6He Wenqiang7Sy Man-Sun8Lu Mingjian9Zhang Huixia10Li Chaoyang11["Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, School of Basic Medical Sciences, University of South China, Hengyang 421001, China","Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["School of Medicine, Pingdingshan University, Pingdingshan 467000, China"]["Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China"]["Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China"]["Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA"]["Department of Interventional Radiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China"]["Department of Human Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"]["Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, School of Basic Medical Sciences, University of South China, Hengyang 421001, China","Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China","Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China"]There are three isoforms of human collagen prolyl 4-hydroxylases (C-P4Hs), each of which has been reported to play an important role in regulating the progression of a variety of human cancers. By analyzing TGCA datasets on human head and neck squamous cell carcinoma (HNSC), we find that a higher expression of all three C-P4HAs (the <sc>α subunit</sc> of C-P4Hs) is a superior prognostic indicator than a higher expression of two or a single C-P4HA. Unexpectedly, some patients with higher levels of three C-P4HAs survive longer than patients whose tumors have lower expression of C-P4HAs. Therefore, there may be molecule(s) that can negate the deleterious effects of overexpressing C-P4HAs during cancer progression. By constructing a functional protein interaction network of <sc>C-P4HAs</sc> and analyzing molecules whose expressions are correlated significantly with that of C-P4HAs, we identify scribble cell polarity complex component 2 (LLGL2) as a factor that antagonizes the effects of overexpressed <sc>C-P4HAs</sc> on HNSC. Silencing of LLGL2 in the human oral squamous cell line Cal-27 upregulates the expression of occludin and increases cancer cell invasion and migration. In contrast, knocking down C-P4HA alone inhibits cell migration and invasion. Furthermore, simultaneously downregulating three C-P4HAs has more pronounced effects on inhibiting cell migration and invasion. Accordingly, high LLGL2 expression is also a marker indicating improved prognosis in patients with HNSC. These results suggest that the interplay between LLGL2 and C-P4HAs may be targeted to mitigate HNSC tumorigenesis and progression. <?Pub Caret 31?>https://www.sciengine.com/doi/10.3724/abbs.2024140HNSCP4HAsLLGL2occludinprognosis |
| spellingShingle | Xu Miao Shi Run Yang Jie Chen Heng Liu Shihua Yu Shupei Li Sasa He Wenqiang Sy Man-Sun Lu Mingjian Zhang Huixia Li Chaoyang Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin Acta Biochimica et Biophysica Sinica HNSC P4HAs LLGL2 occludin prognosis |
| title | Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin |
| title_full | Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin |
| title_fullStr | Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin |
| title_full_unstemmed | Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin |
| title_short | Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin |
| title_sort | collagen prolyl 4 hydroxylase subunit α member induced head and neck squamous cell carcinoma aggressiveness is antagonized by llgl2 via reduced expression of occludin |
| topic | HNSC P4HAs LLGL2 occludin prognosis |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024140 |
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