Alu-derived cis-element regulates tumorigenesis-dependent gastric expression of GASDERMIN B (GSDMB).
GASDERMIN B (GSDMB) belongs to the novel gene family GASDERMIN (GSDM). All GSDM family members are located in amplicons, genomic regions often amplified during cancer development. Given that GSDMB is highly expressed in cancerous cells and the locus resides in an amplicon, GSDMB may be involved in cancer development and/or progression. However, only limited information is available on GSDMB expression in tissues, normal and cancerous, from cancer patients. Furthermore, the molecular mechanisms that regulate GSDMB expression in gastric tissues are poorly understood. We investigated the spatiotemporal expression patterns of GSDMB in gastric cancer patients and the 5' regulatory sequences upstream of GSDMB. GSDMB was not expressed in the majority of normal gastric-tissue samples, and the expression level was very low in the few normal samples with GSDMB expression. Most pre-cancer samples showed moderate GSDMB expression, and most cancerous samples showed augmented GSDMB expression. Analysis of genome sequences revealed that an Alu element resides in the 5' region upstream of GSDMB. Reporter assays using intact, deleted, and mutated Alu elements clearly showed that this Alu element positively regulates GSDMB expression and that a putative IKZF binding motif in this element is crucial to upregulate GSDMB expression.
Komiyama
Hiromitsu
H
Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 111 Yata, Mishima, Shizuoka 411-8540, Japan.
Aoki
Aya
A
Tanaka
Shigekazu
S
Maekawa
Hiroshi
H
Kato
Yoriko
Y
Wada
Ryo
R
Maekawa
Takeo
T
Tamura
Masaru
M
Shiroishi
Toshihiko
T
D017398:Alternative Splicing; D020087:Alu Elements / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000094524:Gasdermins
D051740:Ikaros Transcription Factor; D008156:Luciferases; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C527978:GSDMB protein, human; D000094524:Gasdermins; C497239:IKZF1 protein, human