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

Hyo-Sung Jeon; Yi Young Choi; Junya Fukuoka; Makiko Fujii; Lyudmila A Lyakh; Sang-Hyun Song; William D Travis; Jae Yong Park; Jin Jen

doi:10.1016/j.lungcan.2013.07.015

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

Lung Cancer. 2013 Oct;82(1):24-30. doi: 10.1016/j.lungcan.2013.07.015. Epub 2013 Aug 9.

Authors

Hyo-Sung Jeon¹, Yi Young Choi, Junya Fukuoka, Makiko Fujii, Lyudmila A Lyakh, Sang-Hyun Song, William D Travis, Jae Yong Park, Jin Jen

Affiliation

¹ Department of Biochemistry and Cell biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. Electronic address: jeonh@knu.ac.kr.

PMID: 23932364
DOI: 10.1016/j.lungcan.2013.07.015

Abstract

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.

Keywords: HDAC1; Lung cancer; Prognosis; RB; SNIP1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung / metabolism*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / therapy
Cell Line, Tumor
Disease-Free Survival
Female
Gene Expression
Gene Expression Regulation, Neoplastic
HEK293 Cells
Histone Deacetylase 1 / metabolism*
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Kaplan-Meier Estimate
Lung Neoplasms / metabolism*
Lung Neoplasms / mortality
Lung Neoplasms / therapy
Male
Middle Aged
Multivariate Analysis
Prognosis
Proportional Hazards Models
Protein Binding
RNA-Binding Proteins
Retinoblastoma Protein / genetics*
Retinoblastoma Protein / metabolism
Tissue Array Analysis

Substances

Intracellular Signaling Peptides and Proteins
RNA-Binding Proteins
Retinoblastoma Protein
SNIP1 protein, human
HDAC1 protein, human
Histone Deacetylase 1