机构地区:[1]Hunan Province Key Laboratory of Tumor Cellular&Molecular Pathology,Cancer Research Institute,School of Basic Medical Sciences,University of South China,Hengyang 421001,China [2]Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation,School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou 511436,China [3]School of Medicine,Pingdingshan University,Pingdingshan 467000,China [4]Department of Pathology,School of Medicine,Case Western Reserve University,Cleveland,Ohio 44106,USA [5]Department of Interventional Radiology,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China [6]Department of Human Anatomy,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [7]Guangzhou Institute of Cancer Research,the Affiliated Cancer Hospital,Guangzhou Medical University,Guangzhou 510095,China
出 处:《Acta Biochimica et Biophysica Sinica》2024年第12期1833-1847,共15页生物化学与生物物理学报(英文版)
基 金:supported by the grants from the National Natural Science Foundation of China(Nos.32070147,30670170 and 32470172 to C.L.);the MOST(No.2018YFA0507201 to C.L.),the Science and Technology Program from Forestry Administration of Guangdong(No.2024KJCX020 to C.L.);the Pingdingshan College PhD Startup Fund(No.PXY-BSQD-2024007 to R.S.).
摘 要: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(theαsubunit 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 C-P4HAs 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 C-P4HAs 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.
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