Extracellular domain of semaphorin 5A serves a tumor‑suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells
Journal
International journal of oncology
Journal Volume
60
Journal Issue
2
ISSN
1791-2423
1019-6439
Date Issued
2022-02-01
Author(s)
Chen, Ming Zhen
Su, Li Yu
Ko, Pin Hao
Hsu, Ming Hsuan
Chuang, Li Ling
Abstract
Semaphorin 5A (SEMA5A), which was originally identified as an axon guidance molecule in the nervous system, has been subsequently identified as a prognostic biomarker for lung cancer in nonsmoking women. SEMA5A acts as a tumor suppressor by inhibiting the proliferation and migration of lung cancer cells. However, the regulatory mechanism of SEMA5A is not clear. Therefore, the purpose of the present study was to explore the roles of different domains of SEMA5A in its tumor‑suppressive effects in lung adenocarcinoma cell lines. First, it was revealed that overexpression of full length SEMA5A or its extracellular domain significantly inhibited the proliferation and migration of both A549 and H1299 cells using MTT, colony formation and gap closure assays. Next, microarray analyses were performed to identify genes regulated by different domains of SEMA5A. Among the differentially expressed genes, the most significant function of these genes that were enriched was the 'Interferon Signaling' pathway according to Ingenuity Pathway Analysis. The activation of the 'Interferon Signaling' pathway was validated by reverse transcription‑quantitative PCR and western blotting. In summary, the present study demonstrated that the extracellular domain of SEMA5A could upregulate genes in interferon signaling pathways, resulting in suppressive effects in lung adenocarcinoma cells.
Subjects
extracellular domain
lung cancer
semaphorin 5A
tumor suppressor
SDGs
Other Subjects
SEMA5A protein, human; semaphorin; cell proliferation; drug effect; genetics; human; lung adenocarcinoma; metabolism; signal transduction; tumor cell line; tumor suppressor gene; Adenocarcinoma of Lung; Cell Line, Tumor; Cell Proliferation; Genes, Tumor Suppressor; Humans; Semaphorins; Signal Transduction
Publisher
NLM (Medline)
Type
journal article