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- W4249233022 abstract "Melanoma is one of leading causes of death and its metastasis signals a dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate the steps of metastasis in several cancers, including melanoma. We become interested in a lncRNA named SRA (steroid receptor RNA activator) because it is the first lncRNA that also encodes a conserved protein SRAP and both regulates progression of prostate and breast cancers. We investigated the role of SRA in proliferation, migration, invasion, EMT, and metastasis using B16 melanoma cells transfected with shRNA against SRA. The expression of SRAP was measured in human melanoma tissue and in human and mouse melanoma cells by immunofluorescence and PCR. The result showed that B16 cell proliferation was decreased when SRA was knock down. The migration assay using plate scratching revealed that SRA knock down inhibited the tumor cell migration significantly. Invasion analysis revealed that CCL21, the ligand of CCR7, mediated tumor cell migration was abolished in SRA-deficient B16 cells. In parallel, p38 de-phosphorylation and reciprocally enhanced phosphorylation of bRAF and MEK1/2 were present in B16-SRAi cells. Interesting, the increased expression of EMT markers, b-catenin and n-cadherin, induced by CCL21 was reduced in B16-SRAi cells, suggesting that SRA enhances the EMT process. In vivo experimental metastasis showed that B16-SRAi cells formed significantly less tumor nodules in the lungs grossly and microscopically. In summary, our result showed that SRA product is increased in melanoma tissue and SRA mediates p38 activation, melanoma cell invasion, proliferation, and distant metastasis." @default.
- W4249233022 created "2022-05-12" @default.
- W4249233022 creator A5015134872 @default.
- W4249233022 creator A5084878201 @default.
- W4249233022 date "2019-05-01" @default.
- W4249233022 modified "2023-09-29" @default.
- W4249233022 title "776 Steroid receptor RNA activator (SRA), a long noncoding RNA, activates p38, facilitates epithelial mesenchymal transformation, and experimental melanoma metastasis" @default.
- W4249233022 doi "https://doi.org/10.1016/j.jid.2019.03.852" @default.
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