Hypoxia and hypoxia-inducible factor 1 repress SEMA4B expression to promote non-small cell lung cancer invasion
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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.
KeywordsSema domain of semaphorin 4B Hypoxia-inducible factor 1 Invasion Lung cancer
This work was supported by WU JIE PING Medical foundation. We thanks Dr. Liu Ping from Shanghai Institute of Materia Medica, Chinese Academy of Sciences for her kind assistant about the invasion assay.
Conflicts of interest
- 22.Vadasz Z, Toubi E. Semaphorins: their dual role in regulating immune-mediated diseases. Clin Rev Allergy Immunol 2013. doi: 10.1007/s12016-013-8360-4.