Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma

ABSTRACT: Pheochromocytoma has attracted much attention as a kind of neuroendocrine tumor with the highest genetic correlation in all types of tumors. Detailedly, the frequency of germline mutation in pheochromocytoma is as high as about 40%, and the mutation frequency of von Hippel Lindau (VHL) is the highest in all pheochromocytoma genes. However, the effects of VHL mutation on proteome of pheochromocytoma have remained unexplored. In this study, we compared and analyzed the proteomics of VHL-deficient and VHL WT PC12 cell line. It is showed that expressional level of 434 proteins (fold change > 1.3, VHL shRNA/WT) was significantly changed by VHL deficiency. Furthermore, the functions of these proteins were predicted by gene ontology (GO) and Kyoto Protocol Encyclopedia of Genes and Genomes (KEGG). Of the 434 proteins, 83 proteins, involved in cell proliferation, cell cycle, cell migration, and so on, were interpreted their complex regulatory relationships using String database. More importantly, we discovered 7 novel critical genes whose expression were up-regulated due to VHL deficiency, 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), which may be related to cell proliferation and migration in VHL-mutated pheochromocytoma tumor samples. These results indicate that deficiency of VHL would promote the development of pheochromocytoma by activating expression of genes associated with cell proliferation and migration.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cell Culture

SUBMITTER: Feizhou Zhu  

LAB HEAD: Feizhou Zhu

PROVIDER: PXD021190 | Pride | 2021-03-11

REPOSITORIES: Pride