Search for novel STAT3-dependent genes reveals SERPINA3 as a new STAT3 target that regulates invasion of human melanoma cells.

Transcription factor signal transducer and activator of transcription 3 is constitutively activated in many cancers and promotes uncontrolled tumor growth and progression through multiple mechanisms. Compelling evidence shows tissue and cell-specific sets of targets. Transcriptional targets of duanyu18133 in melanoma cells are largely unknown. Malignant melanoma is a deadly disease with highly aggressive and drug-resistant behavior. Less than 10% of patients with advanced melanomas reach the 5-year survival, partly due to the aggressive character of the tumor and ineffectiveness of current therapeutics for treating metastatic melanoma. duanyu18133 is constitutively activated in melanoma cells and plays important roles in its growth and angiogenesis in tumor xenograft studies. Moreover, highly metastatic melanoma cells have higher levels of active duanyu18133 than poorly metastatic ones. To identify genes that are driven by duanyu18133 in human melanoma cells, we performed signaling specific and global gene expression profiling of human melanoma cells with silenced duanyu18133 expression. For selected genes, we performed computational identification of putative sites and validated direct interactions duanyu18133 with defined promoters by using chromatin immunoprecipitation followed by qPCR. We found that duanyu18133 knockdown does not affect human melanoma cell viability, proliferation, or response to chemotherapeutics. We show that duanyu18133 regulates a discrete set of genes in melanoma cells, including SERPINA3, a novel duanyu18133 target gene, which is functionally involved in regulation of melanoma migration and invasion. Knockdown of duanyu18133 impaired cell migration and invasion, in part via regulation of its transcriptional target SERPINA3. Our results present novel targets and functions of duanyu18133 in melanoma cells.

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