Sema4A Responds to Hypoxia and Is Involved in Breast Cancer Progression
Sema4A Responds to Hypoxia and Is Involved in Breast Cancer Progression
复制标题
Sema4A 对缺氧做出反应并参与乳腺癌进展
DOI：
10.1248/bpb.b18-00423
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Mingyong Han
中科院分区：
文献类型：
--
作者：
Xiao Liu;Yinping Sun;Wei Tian;Fuli Wang;Xiao Lv;Min Wang;Tiantian Sun;Jingjing Zhang;Lin Wang;Mingyong Han
Semaphorin 4A（Sema 4A）是免疫细胞中表达的信号蛋白家族成员，与肿瘤疾病的进展密切相关。本研究旨在探讨Sema 4A在乳腺癌中的表达及其病理学作用。我们的数据显示，Sema 4A.的表达增加，在组织和血清中的BCa患者相比，正常对照。低氧处理可诱导BCa细胞Sema 4A的表达，而沉默低氧诱导因子（HIF）-1α可减弱上述诱导作用。染色质免疫沉淀（ChIP）分析表明，HIF-1α可通过直接与Sema 4A基因启动子结合来调控Sema 4A的表达，低氧刺激可进一步促进Sema 4A基因的富集。此外，沉默Sema 4A还能抑制细胞增殖、血管内皮生长因子（VEGF）的产生以及Akt、细胞外信号调节激酶（ERK）1/2丝裂原活化蛋白激酶的磷酸化。（MAPK）和信号转导及转录激活因子（STAT）3的作用，但在缺氧条件下可诱导BCa细胞凋亡。相比之下，重组人Sema 4A处理显示出相反的效果。综上所述，这些结果表明，Sema 4A可以在缺氧的情况下促进BCa的进展，并且它可能具有作为BCa治疗靶点的潜力。
Semaphorin4A (Sema4A) is a family member of semaphorins expressed in immune cells and is also related with disease progression of tumor disease. In this study, we investigate the expression and pathological role of Sema4A in breast cancer (BCa). Our data showed that the expression of Sema4A.increased in the tissues and serum of BCa patients when compared with normal controls. The expression of Sema4A in BCa cells could be induced by hypoxic treatment, whereas silencing hypoxia-inducible factor (HIF)-1α could attenuate the above induced. Furthermore, chromatin immunoprecipitation (ChIP) analysis demonstrated that HIF-1α could regulate the expression of Sema4A through directly binding to the promoter of Sema4A gene, whose enrichment could be further enhanced by hypoxic stimulation. In addition, silencing Sema4A could inhibit the proliferation, vascular endothelial growth factor (VEGF) production and the phosphorylation of Akt, extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase.(MAPK) and signal transduction and activator of transcription (STAT)3, but induce apoptosis of BCa cells in the presence of hypoxia. In contrast, recombinant human Sema4A treatment showed the opposite effects. Taken together, these results suggest that Sema4A could promote progression of BCa in the presence of hypoxia and it may hold potential for treatment target for BCa.