Format

Send to

Choose Destination
Cancer Genomics Proteomics. 2018 May-Jun;15(3):165-174.

Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma.

Author information

1
Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan saeki@okinawa-nurs.ac.jp.
2
Statistical Genetics Analysis Division, StaGen Co. Ltd., Tokyo, Japan.
3
Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
4
Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan.
5
Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital East, Chiba, Japan.

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.

KEYWORDS:

ChIP-seq; LMO1; Neuroblastoma; pediatric cancer; therapeutic targets; transcription regulator

PMID:
29695398
PMCID:
PMC5971008
DOI:
10.21873/cgp.20074
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center