Semaphorin 4B promotes tumor progression and associates with immune infiltrates in lung adenocarcinoma

癌症研究 腺癌 信号灯 肿瘤微环境 免疫系统 基因沉默 肺癌 体内 CD8型 肿瘤进展 生物 渗透(HVAC) 医学 病理 免疫学 癌症 内科学 受体 生物技术 物理 基因 热力学 生物化学
作者
Jun Jiang,Yuan Lu,Fang Zhang,Tao Pan,Zhipei Zhang,Yi Ching Esther Wan,Xinling Ren,Rui Zhang
出处
期刊:BMC Cancer [Springer Nature]
卷期号:22 (1) 被引量:12
标识
DOI:10.1186/s12885-022-09696-w
摘要

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.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.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.These findings demonstrated SEMA4B might play an oncogenic role in LUAD progression, and be a promising therapeutic target for lung cancer.

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