Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma
Abstract Background Semaphorins have been found to play important roles in multiple malignancy-related processes. However, the role of Semaphorin 4B (SEMA4B) in lung cancer remains unclear. Here, we aimed to explore the biological functions of SEMA4B in through bioinformatic analysis, in vitro and i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09696-w |
| _version_ | 1811248090150076416 |
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| author | Jun Jiang Yuan Lu Fang Zhang Tao Pan Zhipei Zhang Yi Wan Xinling Ren Rui Zhang |
| author_facet | Jun Jiang Yuan Lu Fang Zhang Tao Pan Zhipei Zhang Yi Wan Xinling Ren Rui Zhang |
| author_sort | Jun Jiang |
| collection | DOAJ |
| description | Abstract Background Semaphorins have been found to play important roles in multiple malignancy-related processes. However, the role of Semaphorin 4B (SEMA4B) in lung cancer remains unclear. Here, we aimed to explore the biological functions of SEMA4B in through bioinformatic analysis, in vitro and in vivo assays. In the present study, the possible mechanism by which SEMA4B affected the tumor growth and microenvironment of lung adenocarcinoma (LUAD) were investigated. Methods The expression of SEMA4B in LUAD was analyzed by bioinformatic analysis and verified by the immunohistochemistry staining. The prognostic value of SEMA4B in LUAD was investigated using the Kaplan-Meier survival and Cox’s regression model. After silencing SEMA4B expression, the functions of SEMA4B in LUAD cells were investigated by in vitro experiments, including CCK-8 and plate clone formation. And the effect of SEMA4B on tumor growth and immune infiltration was explored in C57BL/6 mice tumor-bearing models. Results SEMA4B expression was upregulated in LUAD tissues and correlated with later pathological stages and poor prognosis of LUAD patients. Further study found that SEMA4B silencing suppressed the proliferation of lung cancer cells both in vitro and in vivo. Bioinformatic analysis showed that SEMA4B expression was correlated with the increased infiltration of myeloid-derived suppressor cells (MDSCs), T-regs and the decreased infiltration of CD8+ T cell in LUAD. Importantly, in vivo study verified that the infiltration of T-regs and MDSCs in tumor microenvironment (TME) of Xenograft tissues was decreased after SEMA4B silencing. Conclusions These findings demonstrated SEMA4B might play an oncogenic role in LUAD progression, and be a promising therapeutic target for lung cancer. |
| first_indexed | 2024-04-12T15:20:43Z |
| format | Article |
| id | doaj.art-9da0389ac882481aba4b50ef9ace16e0 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T15:20:43Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9da0389ac882481aba4b50ef9ace16e02022-12-22T03:27:26ZengBMCBMC Cancer1471-24072022-06-0122111310.1186/s12885-022-09696-wSemaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinomaJun Jiang0Yuan Lu1Fang Zhang2Tao Pan3Zhipei Zhang4Yi Wan5Xinling Ren6Rui Zhang7Department of Health Service, Base of Health Service, Fourth Military Medical UniversityDepartment of Respiratory and Critical Care Medicine, Zhongda Hospital, Southeast UniversityDepartment of Respiratory and Critical Care Medicine, Xijing Hospital, Fourth Military Medical UniversityDepartment of Respiratory and Critical Care Medicine, Xijing Hospital, Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Health Service, Base of Health Service, Fourth Military Medical UniversityDepartment of Respiratory and Critical Care Medicine, Xijing Hospital, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical UniversityAbstract Background Semaphorins have been found to play important roles in multiple malignancy-related processes. However, the role of Semaphorin 4B (SEMA4B) in lung cancer remains unclear. Here, we aimed to explore the biological functions of SEMA4B in through bioinformatic analysis, in vitro and in vivo assays. In the present study, the possible mechanism by which SEMA4B affected the tumor growth and microenvironment of lung adenocarcinoma (LUAD) were investigated. Methods The expression of SEMA4B in LUAD was analyzed by bioinformatic analysis and verified by the immunohistochemistry staining. The prognostic value of SEMA4B in LUAD was investigated using the Kaplan-Meier survival and Cox’s regression model. After silencing SEMA4B expression, the functions of SEMA4B in LUAD cells were investigated by in vitro experiments, including CCK-8 and plate clone formation. And the effect of SEMA4B on tumor growth and immune infiltration was explored in C57BL/6 mice tumor-bearing models. Results SEMA4B expression was upregulated in LUAD tissues and correlated with later pathological stages and poor prognosis of LUAD patients. Further study found that SEMA4B silencing suppressed the proliferation of lung cancer cells both in vitro and in vivo. Bioinformatic analysis showed that SEMA4B expression was correlated with the increased infiltration of myeloid-derived suppressor cells (MDSCs), T-regs and the decreased infiltration of CD8+ T cell in LUAD. Importantly, in vivo study verified that the infiltration of T-regs and MDSCs in tumor microenvironment (TME) of Xenograft tissues was decreased after SEMA4B silencing. Conclusions These findings demonstrated SEMA4B might play an oncogenic role in LUAD progression, and be a promising therapeutic target for lung cancer.https://doi.org/10.1186/s12885-022-09696-wSEMA4BLung adenocarcinomaImmune infiltrationBioinformaticsPrognosis |
| spellingShingle | Jun Jiang Yuan Lu Fang Zhang Tao Pan Zhipei Zhang Yi Wan Xinling Ren Rui Zhang Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma BMC Cancer SEMA4B Lung adenocarcinoma Immune infiltration Bioinformatics Prognosis |
| title | Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| title_full | Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| title_fullStr | Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| title_full_unstemmed | Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| title_short | Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| title_sort | semaphorin 4b promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma |
| topic | SEMA4B Lung adenocarcinoma Immune infiltration Bioinformatics Prognosis |
| url | https://doi.org/10.1186/s12885-022-09696-w |
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