Gene Set: KIM_LRRC3B_TARGETS

Standard name KIM_LRRC3B_TARGETS
Systematic name M17363
Brief description Immune response genes up-regulated in zenograft tumors formed by SNU-601 cells (gastric cancer) made to express LRRC3B [GeneID=116135].
Full description or abstract Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of LRRC3B, but treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased LRRC3B expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that LRRC3B expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that LRRC3B was significantly hypermethylated in gastric tumors. Stable transfection of LRRC3B in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and LRRC3B expression suppressed tumorigenesis in nude mice. Microarray analysis of LRRC3B-expressing xenograft tumors showed induction of immune response-related genes and IFN signaling genes. H&E-stained sections of LRRC3B-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18757430   Authors: Kim M,Kim JH,Jang HR,Kim HM,Lee CW,Noh SM,Song KS,Cho JS,Jeong HY,Hahn Y,Yeom YI,Yoo HS,Kim YS
Exact source Table 3S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform Human_RefSeq
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Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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