Semaphorin 5A suppresses the proliferation and migration of lung adenocarcinoma cells
Journal
International Journal of Oncology
Journal Volume
56
Journal Issue
1
Pages
165-177
Date Issued
2020
Author(s)
Abstract
Semaphorin 5A (SEMA5A), a member of the semaphorin family, plays an important role in axonal guidance. Previously, the authors identified another possible role of SEMA5A as a prognostic biomarker for non-smoking women with lung adenocarcinoma in Taiwan, and this phenomenon has been validated in other ethnic groups. However, the functional significance of SEMA5A in lung adenocarcinoma remains unclear. Therefore, we assessed the function of SEMA5A in three lung adenocarcinoma cell lines in this study. Kaplan-Meier Plotter for lung cancer was conducted for survival analyses. Reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis were performed to investigate the expression and post-translational regulation of SEMA5A in lung adenocarcinoma cell lines. A pre-designed PyroMark CpG assay and 5-aza-2'-deoxycytidine treatment were used to measure the methylation levels of SEMA5A. The biological functions of lung adenocarcinoma cells overexpressing SEMA5A were investigated by microarrays, and validated both in vitro (proliferation, colony formation and migration assays) and in vivo (tumor xenografts) experiments. The results revealed that the hypermethylation of SEMA5A and the cleavage of the extracellular domain of SEMA5A were responsible for the downregulation of the SEMA5A levels in lung adenocarcinoma cells (A549 and H1299) as compared to the normal controls. Functional analysis of SEMA5A-regulated genes revealed that they were involved in cellular growth and proliferation. The overexpression of SEMA5A in A549 and H1299 cells significantly decreased the proliferation (P<0.01), colony formation (P<0.001) and migratory ability (P<0.01) of the cells. The suppressive effects of SEMA5A on the proliferative and migratory ability of the cells were also observed in both in vitro and in vivo experiments using brain metastatic Bm7 lung adenocarcinoma cells. On the whole, the findings of this study suggest a suppressive role for SEMA5A in lung adenocarcinoma involving the inhibition of the proliferation and migration of lung transformed cells. ? 2020 Spandidos Publications. All rights reserved.
SDGs
Other Subjects
semaphorin; semaphorin 5A; unclassified drug; SEMA5A protein, human; semaphorin; tumor marker; A-549 cell line; animal experiment; animal model; Article; cell growth; cell migration; cell proliferation; controlled study; DNA methylation; gene control; human; human cell; in vitro study; in vivo study; lung adenocarcinoma; male; mouse; NCI-H1299 cell line; nonhuman; overall survival; priority journal; protein cleavage; protein expression; SEMA5A gene; tumor xenograft; animal; apoptosis; Bagg albino mouse; cell motion; drug screening; gene expression regulation; genetics; lung adenocarcinoma; lung tumor; metabolism; nude mouse; pathology; prognosis; survival rate; tumor cell culture; tumor invasion; Adenocarcinoma of Lung; Animals; Apoptosis; Biomarkers, Tumor; Cell Movement; Cell Proliferation; DNA Methylation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Prognosis; Semaphorins; Survival Rate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
Publisher
Spandidos Publications
Type
journal article