Jian Hong, Liu Bin, Zhang Jie
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Tumour Biol. 2014 May;35(5):4949-55. doi: 10.1007/s13277-014-1651-4. Epub 2014 Jan 29.
Sema domain of semaphorin 4B (SEMA4B), which is an interacting protein of LNM35, plays an important role in lung cancer invasion. However, the regulation mechanism of this protein is completely unknown. Here, we report that hypoxia and hypoxia mimic reagent could downregulate the expression of SEMA4B in human non-small cell lung cancer (NSCLC) lines. We provide evidences that SEMA4B is a direct target of hypoxia-inducible factor 1 (HIF-1). Silencing the expression of HIF-1α in cancer cells by RNA interference abolished hypoxia-repressed SEMA4B expression. Using luciferase reporter assay, we showed that HIF-1α recognized a hypoxia-responsive element (HRE) of SEMA4B gene, which is required for HIF-1-repressed SEMA4B expression. Moreover, ectopic expression of SEMA4B abolished invasion of hypoxia-induced NSCLC cells. Taken together, these data would shed novel insights on the mechanisms for invasion of hypoxia-induced NSCLC cells.
信号素4B（SEMA4B）的信号素结构域作为LNM35的一种相互作用蛋白，在肺癌侵袭中发挥重要作用。然而，这种蛋白质的调控机制完全未知。在此，我们报道缺氧和缺氧模拟试剂可下调人非小细胞肺癌（NSCLC）细胞系中SEMA4B的表达。我们提供证据表明SEMA4B是缺氧诱导因子1（HIF-1）的直接靶点。通过RNA干扰沉默癌细胞中HIF-1α的表达可消除缺氧抑制的SEMA4B表达。利用荧光素酶报告基因检测，我们发现HIF-1α识别SEMA4B基因的缺氧反应元件（HRE），这是HIF-1抑制SEMA4B表达所必需的。此外，SEMA4B的异位表达消除了缺氧诱导的NSCLC细胞的侵袭。综上所述，这些数据将为缺氧诱导的NSCLC细胞侵袭机制提供新的见解。
