Extracellular domain of semaphorin 5A serves a tumor‑suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells

Chen,Ming-Zhen; Su,Li-Yu; Ko,Pin-Hao; Hsu,Ming-Hsuan; Chuang,Li-Ling; Chen,Li-Han; Lu,Tzu-Pin; Chuang,Eric Y.; Chow,Lu-Ping; Tsai,Mong-Hsun; Hsu,Hsao-Hsun; Lai,Liang-Chuan

doi:10.3892/ijo.2022.5311

Extracellular domain of semaphorin 5A serves a tumor‑suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells

Authors:
- Ming-Zhen Chen
- Li-Yu Su
- Pin-Hao Ko
- Ming-Hsuan Hsu
- Li-Ling Chuang
- Li-Han Chen
- Tzu-Pin Lu
- Eric Y. Chuang
- Lu-Ping Chow
- Mong-Hsun Tsai
- Hsao-Hsun Hsu
- Liang-Chuan Lai
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Affiliations: Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, R.O.C., Department of Traditional Chinese Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan, R.O.C., School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, R.O.C., Institute of Fisheries Science, College of Life Science, National Taiwan University, Taipei 106, Taiwan, R.O.C., Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei 106, Taiwan, R.O.C., Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei 106, Taiwan, R.O.C., Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 106, Taiwan, R.O.C., Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan, R.O.C.
Published online on: January 19, 2022 https://doi.org/10.3892/ijo.2022.5311
Article Number: 21

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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.

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