Literature DB >> 29710483

DNMT1/miR-200a/GOLM1 signaling pathway regulates lung adenocarcinoma cells proliferation.

Longqiu Yang1, Pengcheng Luo2, Qiong Song3, Xuejie Fei4.   

Abstract

OBJECTIVES: Lung adenocarcinoma (LAD) comprises about 80% of all diagnosed lung cancers. However, the underlying regulatory mechanism of LAD cell proliferation is largely unclear. The emergence of microRNAs and molecular-targeted therapies adds a new dimension in our efforts to combat this deadly disease.
METHOD: In this work, the A549 and H1650 human lung cancer cell lines were used in this study. The proliferation was evaluated by the MTT and BrdU assay. The expression level of related proteins was detected by western blot. RESULT: We reported GOLM1 was highly expressed in LAD cells and associated with low survival ratio and higher grade malignancy. Knockdown of GOLM1 repressed the LAD cell proliferation. Overexpression of GOLM1 promoted the cell proliferation. Further we found that the level of microRNA-200a (miR-200a) expression was low in LAD cells. miR-200a repress GOLM1 expression by directly targeting its 3? UTR. Overexpression of miR-200a repressed the cell proliferation and blocked the increase of LAD cell proliferation caused by GOLM1 overexpression. Further, we found that miR-200 was downregulated by DNMT1.Overexpression of DNMT1 blocked the function of miR-200a on repressing proliferation. We then found that knockdown of DNMT1 repressed LAD cell proliferation, which could be rescued by GOLM1 overexpression.
CONCLUSION: This work revealed the critical function of GOLM1/miR-200a/DNMT1 signaling pathway on regulating LAD cell proliferation, and might lay the foundation for further clinical treatment of LAD.
Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Entities:  

Keywords:  Cell proliferation; DNMT; GOLM1; Lung adenocarcinoma; miR-200a

Mesh:

Substances:

Year:  2018        PMID: 29710483     DOI: 10.1016/j.biopha.2018.01.161

Source DB:  PubMed          Journal:  Biomed Pharmacother        ISSN: 0753-3322            Impact factor:   6.529


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