RT Journal Article
SR Electronic
T1 Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 165
OP 174
VO 15
IS 3
A1 NORIHISA SAEKI
A1 AKIRA SAITO
A1 YUKI SUGAYA
A1 MITSUHIRO AMEMIYA
A1 HIROE ONO
A1 RIE KOMATSUZAKI
A1 KAZUYOSHI YANAGIHARA
A1 HIROKI SASAKI
YR 2018
UL http://cgp.iiarjournals.org/content/15/3/165.abstract
AB 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.