Effects of let-7e on LPS-Stimulated THP-1 Cells Assessed by iTRAQ Proteomic Analysis

Lian Gui, Qianqian Zhang, Yan Cai, Xiaohong Deng, Yingke Zhang, Cheukfai Li, Qi Guo, Xiaoshun He, Junqi Huang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose: Previous studies have demonstrated that let-7e is associated with inflammatory responses. To date, the roles and mechanisms of let-7e have not been completely revealed.Therefore, we aim to identify proteins associated with let-7e overexpression and explore their functions in the immune responses, including in cytokine production. Experimental design: High-throughput isobaric tag for relative and absolute quantitation (iTRAQ) technology is used to provide the first genome-wide study of THP-1 cells transfected with let-7e mimic followed by lipopolysaccharide (LPS) stimulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and KEGG pathway enrichment analyses are used to analyze a large number of differentially expressed proteins (DEPs) associated with let-7e overexpression or LPS stimulation. Quantitative reverse transcription PCR (qRT-PCR) and 50% tissue culture infective dose (TCID50) assays are processed to confirm the relationship of let-7e and dengue virus replication. Results: iTRAQ results show that let-7e is associated with the expression of anti-viral proteins. What's more, calcineurin subunit B type 1, an anti-tumor factor, is upregulated by let-7e after LPS stimulation. KEGG analyses identify that some DEPS associated with let-7e overexpression are involved in the measles and influenza A pathways, and LPS-stimulated proteins in THP-1 cells are mainly enriched in transcriptional misregulation in cancer pathway and hippo signaling pathway (multiple species). The results of qRT-PCRand TCID50 show that let-7e promotes dengue virus replication, which is in agreement with the iTRAQ results. Conclusions and clinical relevance: These results provide molecular insights into the regulatory mechanisms of let-7e in cytokine expression, virus replication, and anti-tumor function.

Original languageEnglish (US)
Article number1700012
JournalProteomics - Clinical Applications
Volume12
Issue number5
DOIs
StatePublished - Sep 2018

Keywords

  • Cytokines
  • Proteomic
  • Virus
  • let-7e

ASJC Scopus subject areas

  • Clinical Biochemistry

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