Aug 6, 2020

Epigenetic Silencing of LMX1A Contributes to Cancer Progression in Lung Cancer Cells

International Journal of Molecular Sciences
Ti-Hui WuYa-Wen Lin

Abstract

Epigenetic modification is considered a major mechanism of the inactivation of tumor suppressor genes that finally contributes to carcinogenesis. LIM homeobox transcription factor 1α (LMX1A) is one of the LIM-homeobox-containing genes that is a critical regulator of growth and differentiation. Recently, LMX1A was shown to be hypermethylated and functioned as a tumor suppressor in cervical cancer, ovarian cancer, and gastric cancer. However, its role in lung cancer has not yet been clarified. In this study, we used public databases, methylation-specific PCR (MSP), reverse transcription PCR (RT-PCR), and bisulfite genomic sequencing to show that LMX1A was downregulated or silenced due to promoter hypermethylation in lung cancers. Treatment of lung cancer cells with the demethylating agent 5-aza-2'-deoxycytidine restored LMX1A expression. In the lung cancer cell lines H23 and H1299, overexpression of LMX1A did not affect cell proliferation but suppressed colony formation and invasion. These suppressive effects were reversed after inhibition of LMX1A expression in an inducible expression system in H23 cells. The quantitative RT-PCR (qRT-PCR) data showed that LMX1A could modulate epithelial mesenchymal transition (EMT) through E-cad...Continue Reading

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Mentioned in this Paper

Fibronectins
Cell Proliferation
ED-B fibronectin protein, human
CDH1 protein, human
Epigenetic Process
Cancer Progression
Hypermethylation
Gene Expression Analysis
Lmx1a protein, mouse
Non-Small Cell Lung Carcinoma

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