High expression of SNIP1 correlates with poor prognosis in non-small cell lung cancer and SNIP1 interferes with the recruitment of HDAC1 to RB in vitro.
The Rb tumor suppressor gene performs a critical role in controlling cell proliferation and tumorigenesis; it recruits HDAC1 protein into the E2F complexes to repress transcription. In this study, we demonstrate that SNIP1, RB and HDAC1 were significantly expressed in same lung cancer tissues in a tissue microarray (TMA) containing 300 non-small cell lung cancers (NSCLC). High expression level of SNIP1 in tumor patients was significantly correlated with poor prognosis in NSCLC (log-rank P for OS = 0.01, log-rank P for DFS = 0.001). Functionally, SNIP1 competes with HDAC1 for binding to RB and reduces HDAC activity in vitro. Knockdown of SNIP1 reduced colony formation ability of lung cancer cells. These findings may indicate the involvement of SNIP1 in progression of lung cancer by regulating the RB/HDAC1 interaction.
Department of Biochemistry and Cell biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. Electronic address: jeonh@knu.ac.kr.
Hyo-Sung
HS
Jeon
Yi Young
YY
Choi
Junya
J
Fukuoka
Makiko
M
Fujii
Lyudmila A
LA
Lyakh
Sang-Hyun
SH
Song
William D
WD
Travis
Jae Yong
JY
Park
Jin
J
Jen
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; C411545:SNIP1 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
HDAC1; Lung cancer; Prognosis; RB; SNIP1