MTA1 gene silencing inhibits invasion and alters the microRNA expression profile of human lung cancer cells

Abstract

Abstract. Metastasis-associated gene 1 (MTA1) is involved in the carcinogenesis and metastasis of many human carcinomas. However, its exact role in non-small cell lung cancer (NSCLC) is still unclear. Using immunohistochemistry analysis, we recently identified MTA1 to be associated with the progression of NSCLC. Here, we carried out further analysis on the effect of MTA1 knockdown in an NSCLC cell line on cell functions and the global microRNA (miRNA) expression profile. We succeeded in establishing the MTA1 knockdown NSCLC cell line using RNA interference (RNAi), and found that the silencing of MTA1 resulted in the effective inhibition of the invasive ability of NSCLC cells, but not of the cell growth in vitro. We performed an miRNA microarray analysis and demonstrated for the first time that MTA1 knockdown significantly changed the expression of some miRNAs in NSCLC cells. Among them, some have a well-characterized association with cancer progression, e.g. miR-125b, miR-210, miR-103, miR-194 and miR-500. In summary, it is evident from our results that MTA1 functions in regulating the invasive phenotype of lung cancer cells and this regulation may be through altered miRNA expression. The interaction between MTA1 and the miRNAs which contributes to lung cancer is worthy of further investigation.

Structure, expression and functions of MTA genes

“…In addition, MTA1 may also influence the status of cellular genes indirect through a microRNA network as depletion of MTA1 in cancer cells alters the levels of miR-210, miR-125b, miR-194, miR-103, and miR-500 (Zhu et al, 2012b; Li et al, 2013c). …”

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

“…Overexpression of MTA1 is significantly associated with tumor progression and poor prognosis in NSCLC cells [15], and it has been demonstrated that the overexpression of MTA1 protein is common in early-stage NSCLC and is obviously related to tumor angiogenesis and poor survival [16]. A previous study demonstrated that MTA1 plays a key role in the regulation and mediation of the invasive phenotypes of lung cancer cells, and it has been reported that this regulation functions by altering the expression of miR [14]. However, the mechanism by which MTA1 protein regulates the malignant progression of NSCLC is not well understood [17].…”

“…In addition, a previous study demonstrated that miR-183 could repress epithelial-mesenchymal transition (EMT) and invasion of human pancreatic cancer cells by inhibiting the expression of MTA1 [13]. MTA1 is the founding member of the MTA family of coregulatory factors in transcriptional programs, and plays an integral role in nucleosome remodeling and histone deacetylation (NuRD) [14]. Overexpression of MTA1 is significantly associated with tumor progression and poor prognosis in NSCLC cells [15], and it has been demonstrated that the overexpression of MTA1 protein is common in early-stage NSCLC and is obviously related to tumor angiogenesis and poor survival [16].…”

GLNMDA: a novel method for miRNA-disease association prediction based on global linear neighborhoods

“…Among the five unconfirmed miRNAs, hsa-miR-499 has been found that the rs3746444T> C polymorphism in its mature sequence could contribute to poor prognosis by modulating cancer-related gene expression and thus involve in the tumorigenesis of LN[51]. Besides, studies have shown that miR-103 was able to promote proliferation of small cell lung cancer cells through targeting MED26 mRNA 3ʹ-UTR[52]. …”