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Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways.

ABSTRACT: Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer?associated mortality in the world and accounts for ~85% of human lung cancers. Metastasis?associated protein 2 (MTA2) is a component of the histone deacetylase complex and serves a role in tumor progression; however, the mechanism through which MTA2 is involved in the progression of NSCLC remains unclear. The aim of the present study was to investigate the expression and function of MTA2 and the MTA2?mediated signaling pathway in NSCLC cells. Expression of MTA2 and its target genes was analyzed in MTA2?overexpressing and anti?MTA2 antibody (AbMTA2)?treated NSCLC cells, as well as growth, migration, invasion and apoptotic?resistance. The inhibitory effects on tumor formation were analyzed using AbMTA2?treated NSCLC cells and in a mouse model. Histological assessment was conducted to analyze the expressions levels of extracellular signal?regulated kinase (ERK), RAC?? serine/threonine protein kinase (AKT) and vascular endothelial growth factor (VEGF) in experimental tumors. Results of the present study demonstrated that MTA2 was overexpressed in NSCLC cells. The growth, migration and invasion of NSCLC cells were markedly inhibited by AbMTA2. In addition, it was observed that the ERK/AKT and VEGF signaling pathways were both upregulated in MTA2?overexpressing NSCLC cells, and downregulated following silencing of MTA2 activation. ERK and AKT phosphorylation levels were downregulated in NSCLC cells and tumors following MTA2 silencing. The in vivo study demonstrated that tumor growth was markedly inhibited following siRNA?MTA2 treatment. In conclusion, the results of the present study suggested that MTA2 silencing may significantly inhibit the growth and aggressiveness of NSCLC cells. Results from the present study indicated that the mechanism underlying the MTA2?mediated invasive potential of NSCLC cells involved the ERK/AKT and VEGF signaling pathways, which may be a potential therapeutic target for the treatment of NSCLC.

SUBMITTER: Zhang B

PROVIDER: S-EPMC5865949 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways.

Zhang Bin B Tao Feng F Zhang Hao H

Molecular medicine reports 20180201 4

Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer‑associated mortality in the world and accounts for ~85% of human lung cancers. Metastasis‑associated protein 2 (MTA2) is a component of the histone deacetylase complex and serves a role in tumor progression; however, the mechanism through which MTA2 is involved in the progression of NSCLC remains unclear. The aim of the present study was to investigate the expression and function of MTA2 and the MTA2‑mediated signaling path ...[more]

PMID: 29393472

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Project description:PurposeThis study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC.MethodsCircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings.ResultsA total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models.ConclusionOur study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.

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Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways.

Publications

Metastasis-associated protein 2 promotes the metastasis of non-small cell lung carcinoma by regulating the ERK/AKT and VEGF signaling pathways.

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