MIER3 suppresses the progression of non-small cell lung cancer by inhibiting Wnt/β-Catenin pathway and histone acetyltransferase activity

Hongye Zhang, Ling Wang, Juan Bai, Wenyu Jiao, Mingxia Wang

Abstract

Background: The mesoderm induction early response 1, family member 3 (MIER3) gene has been recognized as potentially being associated with cancer. However, in relation to the development of non-small cell lung cancer (NSCLC), the expression pattern and the role of MIER3 are yet to be reported. The aim of this research was to investigate the rate of expression of MIER3 in NSCLC cells and tissues and to investigate the role of MIER3 in NSCLC.
Methods: Seventeen patients received NSCLC tissues and corresponding healthy tissues. MTT assay was used to determine cell proliferation. For detecting mRNA and protein expression, we used both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot method. To measure cell apoptosis and cell cycle distribution, we applied the flow cytometry technique. We used a wound-healing assay and a Transwell invasion assay to study cell migration and invasion.
Results: In comparison with adjacent normal tissues, the expression of MIER3 was down-regulated in NSCLC tissues. In addition, the level of MIER3 in NSCLC cell lines was also lower than in pulmonary epithelial cell BEAS-2B. Moreover, when MIER3 was overexpressed, cell proliferation, migration, and invasion were significantly inhibited, apoptosis increased, and cell cycle arrest was induced in A549 and H460 cells. MIER3 overexpression also suppressed tumor growth in NSCLC xenograft mouse models. Furthermore, our study demonstrated that MIER3 down-regulated the Wnt/β-catenin signaling pathway in NSCLC cells. More importantly, MIER3 decreased the activity of histone acetyltransferase (HAT) p300, which may have contributed to its regulation on β-catenin and tumorigenesis.
Conclusions: The data suggests MIER3 takes on the tumor-suppressor role in the progression of NSCLC and, therefore, could prove to be a valuable clinical marker in the prognosis of the disease.