RRC ID 52685
Author Saeki N, Saito A, Sugaya Y, Amemiya M, Ono H, Komatsuzaki R, Yanagihara K, Sasaki H.
Title Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma.
Journal Cancer Genomics Proteomics
Abstract BACKGROUND/AIM:Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed.
MATERIALS AND METHODS:We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines.
RESULTS:We identified three genes regulated by LMO1 in the cells, LIM and senescent cell antigen-like domains 1 (LIMS1), Ras suppressor protein 1 (RSU1) and relaxin 2 (RLN2). LIMS1 and RSU1 encode proteins functioning with integrin-linked kinase (ILK), and inhibition of LIMS1, ILK or RLN2 by shRNA reduced cell proliferation of the NB cells, which was also suppressed with an ILK inhibiting compound Cpd 22.
CONCLUSION:The downstream of LMO1-regulatory cascade includes a tumor-promoting LIMS1/ILK pathway, which has a potential to be a novel therapeutic target.
Volume 15(3)
Pages 165-174
Published 2018-1-1
DOI 10.21873/cgp.20074
PII 15/3/165
PMID 29695398
PMC PMC5971008
MeSH Adaptor Proteins, Signal Transducing / antagonists & inhibitors Adaptor Proteins, Signal Transducing / genetics* Cell Proliferation Chromatin Immunoprecipitation / methods* DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics* Gene Expression Regulation, Neoplastic* High-Throughput Nucleotide Sequencing / methods* Humans LIM Domain Proteins / antagonists & inhibitors LIM Domain Proteins / genetics* Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics Neuroblastoma / genetics* Neuroblastoma / metabolism Neuroblastoma / pathology Protein Serine-Threonine Kinases / antagonists & inhibitors Protein Serine-Threonine Kinases / genetics* RNA, Small Interfering / genetics Signal Transduction Transcription Factors / antagonists & inhibitors Transcription Factors / genetics* Tumor Cells, Cultured
IF 3.147
Times Cited 3
Resource
Human and Animal Cells LA-N-5(RCB0485)