Open AccessPaired box 5 is a frequently methylated lung cancer tumour suppressor gene interfering β‐catenin signalling and GADD 45G expression
Author(s) -
Zhao Lijuan,
Li Shuman,
Gan Lin,
Li Chunhong,
Qiu Zhu,
Feng Yixiao,
Li Jisheng,
Li Lili,
Li Chen,
Peng Weiyan,
Xu Can,
Wang Zhenyu,
Hui Tianli,
Ren Guosheng,
Tao Qian,
Xiang Tingxiu
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12768
Subject(s) - biology , cancer research , ectopic expression , dna methylation , pax5 , lung cancer , methylation , carcinogenesis , cell growth , microbiology and biotechnology , cancer , gene expression , cell culture , transcription factor , pathology , gene , medicine , genetics
Recent studies suggest that paired box 5 ( PAX 5) is down‐regulated in multiple tumours through its promoter methylation. However, the role of PAX 5 in non‐small cell lung cancer ( NSCLC ) pathogenesis remains unclear. The aim of this study is to examine PAX 5 expression, its methylation status, biological functions and related molecular mechanism in NSCLC . We found that PAX 5 was widely expressed in normal adult tissues but silenced or down‐regulated in 88% (7/8) of NSCLC cell lines. PAX 5 expression level was significantly lower in NSCLC than that in adjacent non‐cancerous tissues ( P = 0.0201). PAX 5 down‐regulation was closely associated with its promoter hypermethylation status and PAX 5 expression could be restored by demethylation treatment. Frequent PAX 5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types ( P = 0.006). Ectopic expression of PAX 5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration/invasion as well as tumorigenicity in nude mice. Restoration of PAX 5 expression resulted in the down‐regulation of β‐catenin and up‐regulation of tissue inhibitors of metalloproteinase 2, GADD 45G in lung tumour cells. In summary, PAX 5 was found to be an epigenetically inactivated tumour suppressor that inhibits NSCLC cell proliferation and metastasis, through down‐regulating the β‐catenin pathway and up‐regulating GADD 45G expression.