Open AccessEpigenetic Silencing of TMEM176A Activates ERK Signaling in Human Lung Cancer
Author(s) -
Liming Hu,
Fuyou Zhou,
Hongxia Li,
James G. Herman,
Liming Hu,
Mingzhou Guo,
Tao He
Publication year - 2020
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
ISSN - 2674-3000
DOI - 10.31487/j.jso.2020.02.03
Subject(s) - methylation , lung cancer , cancer research , dna methylation , gene silencing , cell growth , epigenetics , cell , microbiology and biotechnology , cell culture , apoptosis , medicine , biology , gene expression , pathology , gene , biochemistry , genetics
Background: The function of TMEM176A in human lung cancer remains to be elucidated.Materials & Methods: Nine cell lines and 123 cases of lung cancers were employed.Results: TMEM176A was highly expressed in H727 cells, reduced expression was observed in A549, H446and H460 cells, loss of expression was found in H157, H1563, H358, H1299 and H23 cells. TMEM176Awas unmethylated in H727 cells, partially methylated in A549, H446 and H460 cells, and fully methylatedin H157, H1563, H358, H1299 and H23 cells. Loss of/reduced expression of TMEM176A is correlated topromoter region methylation. Restoration of TMEM176A expression was induced by 5-AZA-2-deoxycytidine in complete methylated cells, increased expression of TMEM176A was observed in partiallymethylated cells. These results suggest that TMEM176A is regulated by promoter region methylation inlung cancer cells. TMEM176A was methylated in 53.66% (66/123) of non-small cell lung cancers(NSCLCs) samples. Reduced expression of TMEM176A was associated with promoter region methylationin 40 cases of matched primary NSCLCs and adjacent tissue samples (P<0.05). TMEM176A expressioninduced cell apoptosis, inhibited colony formation, cell proliferation, migration and invasion.Conclusion: Methylation of TMEM176A activated ERK signaling in lung cancer cells. TMEM176Asuppressed human lung cancer cell xenograft growth in mice.