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Microarray analysis of lung cancer cells gene expression in overexpressing different semaphorin 5a domains

ABSTRACT: Semaphorin 5A (SEMA5A) is one member of semaphorin family, which was identified as an axon guidance molecule in nervous systems. In our previous studies, SEMA5A was identified as a prognostic biomarker for lung cancer in nonsmoking women and acted as a tumor suppressor gene in inhibiting the proliferation and migration of lung cancer cells. Yet, the regulatory mechanism of SEMA5A was not clear. Therefore, the purpose of this study was to explore the roles of different domains of SEMA5A on the tumor suppressive effects in lung cancer cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157062 | GEO | 2023/08/19

REPOSITORIES: GEO

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Project description:Semaphorins are a large family of evolutionary conserved morphogenetic signals originally identified as repelling cues in axonal guidance. Intriguingly, Semaphorins have recently been implicated to play a role in cancer progression. In particular, Semaphorin 3B (SEMA3B) is considered a putative tumor suppressor, and yet we found that it is expressed at high levels in many invasive and metastatic human cancers. By investigating experimental tumor models, we confirmed that SEMA3B expression inhibited tumor growth, whereas metastatic dissemination was surprisingly increased. Interestingly, we found that SEMA3B induced the production of Interleukin-8 (IL-8) by tumor cells, by activating p38-MAPK pathway, in a Neuropilin-1 dependent manner. Further, by silencing the expression of endogenous SEMA3B in tumor cells, IL-8 transcription was impaired. The release of IL-8, in turn, induced tumor-associated macrophage recruitment and metastatic dissemination to the lung that could be rescued by using neutralizing antibodies against IL-8. In conclusion, we report here that SEMA3B plays unexpected functions in cancer progression, as it fosters a pro-metastatic environment, through elevated IL-8 secretion and recruitment of macrophages, coupled to suppression of tumor growth. By performing micro-array analysis of gene expression on mRNA derived from MDA-MB-435 cells transduced with SEMA3B or control Empty Vector (EV), we found that one of the most regulated genes was Interleukin-8 (IL-8) (p< 0.001). Interestingly, IL-8 is known to be a chemo-attractant for leucocytes, endothelial and smooth muscle cells, further implicated in human cancer biology. We thus confirmed micro-array data by real-time quantitative PCR in tumor cell lines transduced with SEMA3B: i.e. A549 lung carcinoma, HeLa cervical carcinoma, HT29 colon carcinoma, and GTL16 gastric carcinoma. In addition, western blotting revealed that IL-8 secretion was strongly induced upon SEMA3B expression. Moreover, IL-8 protein levels were specifically up-regulated by treatment with doxycycline in A549 carcinoma cells expressing SEMA3B under control of a drug-inducible promoter. Keywords: Cell type comparison

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Microarray analysis of lung cancer cells gene expression in overexpressing different semaphorin 5a domains

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