[Quantitative proteomics and differential signal enrichment in nasopharyngeal carcinoma cells with or without SETD2 gene knockout].

Abstract

OBJECTIVE\nTo analyze the effects of alterations in the expressions of methyltransferase SETD2 on protein expression profiles in human nasopharyngeal carcinoma (NPC) cells and enrich the differential signaling pathways.\n\n\nMETHODS\nThe total protein was extracted from SETD2-knockout cell line CNE1SETD2-KO and the wild-type cell line CNE1WT, and the differentially expressed proteins were screened by tandem mass tag (TMT) labeled protein quantification technique and tandem mass spectrometry. GO analysis was used to annotate and enrich the differentially expressed proteins, and the KEGG database was used to enrich and analyze the pathways of the differential proteins.\n\n\nRESULTS\nWith a fold change (FC)≥1.2 and P < 0.05 as the screening standard, 2049 differentially expressed proteins were identified in CNE1SETD2-KO cells, among which 904 were up-regulated and 1145 were down-regulated. GO functional annotation results indicated that SETD2 knockout caused characteristic changes in multiple biological processes (cell processes and regulation, cell movement, metabolic processes, and biosynthesis of cellular components), molecular functions (catalytic activity and molecular binding, transcription factor activity), and cellular components (cell membrane, organelle, macromolecular complex). KEGG analysis showed that the differentially expressed proteins were involved in an array of signaling pathways closely related to tumors, including MAPK, PI3K-Akt, Ras, Rap1, mTOR, Hippo, HIF-1, Wnt, AMPK, FoxO, ErbB, P53 and JAK-STAT.\n\n\nCONCLUSIONS\nSETD2 knockout significantly changes the protein expression characteristics of NPC cells and affects a number of signal pathways closely related to tumors. The results provide evidence for investigation of the pathogenesis and therapeutic target screening of NPC.