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Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma
- Source :
- Frontiers in Endocrinology, Frontiers in Endocrinology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Pheochromocytoma, as a neuroendocrine tumor with the highest genetic correlation in all types of tumors, has attracted extensive attention. Von Hipper Lindau (VHL) has the highest mutation frequency among the genes associated with pheochromocytoma. However, the effect of VHL on the proteome of pheochromocytoma remains to be explored. In this study, the VHL knockdown (VHL-KD) PC12 cell model was established by RNA interference (shRNA). We compared the proteomics of VHL-KD and VHL-WT PC12 cell lines. The results showed that the expression of 434 proteins (VHL shRNA/WT > 1.3) changed significantly in VHL-KD-PC12 cells. Among the 434 kinds of proteins, 83 were involved in cell proliferation, cell cycle and cell migration, and so on. More importantly, among these proteins, we found seven novel key genes, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2), and Serpin Family E Member 1 (SERPINE1), were overexpressed and simultaneously regulated cell proliferation and migration in VHL-KD PC12 cells. Furthermore, the abnormal accumulation of HIF2α caused by VHL-KD significantly increased the expression of these seven genes during hypoxia. Moreover, cell-counting, scratch, and transwell assays demonstrated that VHL-KD could promote cell proliferation and migration, and changed cell morphology. These findings indicated that inhibition of VHL expression could promote the development of pheochromocytoma by activating the expression of cell proliferation and migration associated genes.
- Subjects :
- 0301 basic medicine
endocrine system diseases
collagen type III alpha 1 chain (COL3A1)
Syntenins
Endocrinology, Diabetes and Metabolism
Adrenal Gland Neoplasms
Syndecan binding
Pheochromocytoma
Biology
Cell morphology
urologic and male genital diseases
lcsh:Diseases of the endocrine glands. Clinical endocrinology
Von Hippel-Lindau (VHL)
03 medical and health sciences
0302 clinical medicine
Endocrinology
Cell Movement
Humans
syndecan binding protein (SDCBP)
neoplasms
Original Research
Cell Proliferation
lcsh:RC648-665
Cell growth
cellular communication network factor 1 (CCN1)
Connective Tissue Growth Factor
Cell migration
serpin family E member 1 (SERPINE1)
Cell cycle
Molecular biology
female genital diseases and pregnancy complications
CTGF
Collagen Type I, alpha 1 Chain
Collagen, type I, alpha 1
030104 developmental biology
Collagen Type III
Cell culture
connective tissue growth factor (CTGF)
Von Hippel-Lindau Tumor Suppressor Protein
030220 oncology & carcinogenesis
Mutation
collagen type V alpha 2 chain (COL5A2)
Collagen Type V
Cysteine-Rich Protein 61
Subjects
Details
- Language :
- English
- ISSN :
- 16642392
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Endocrinology
- Accession number :
- edsair.doi.dedup.....496f1cd4923f25d892d5842b5d7b5bc8