Hong, Ho, Lee (2020) Steroid receptor RNA activator (SRA), a long noncoding RNA, activates p38, facilitates epithelial mesenchymal transformation, and experimental melanoma metastasis The Journal of investigative dermatology ()


Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We become interested in a lncRNA, SRA (steroid receptor RNA activator), because it is the first lncRNA also encoding a conserved protein SRAP and regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, EMT, and metastasis by RNA interference. The expression of SRAP was measured in melanoma tissue and in human and mouse B16 melanoma cells by immunofluorescence and PCR. The result showed that SRA knock down decreased B16 cell and A375 cell proliferation and it inhibited B16 cell migration significantly. Transwell analysis revealed that CCL21-mediated invasion was abolished in SRA-deficient B16 cells. In parallel, p38 de-phosphorylation and reciprocally phosphorylation of bRAF and MEK1/2 were present in B16-SRAi cells. Interestingly, the induction of EMT markers, β-catenin and n-cadherin, by CCL21 was reduced in B16-SRAi cells, suggesting that SRA promotes EMT process. In vivo experimental metastasis showed that B16-SRAi cells formed significantly less tumor nodules in lungs grossly and microscopically. In summary, our result showed that SRA expression is increased in melanoma tissue and that SRA mediates p38 activation, cell invasion, proliferation, regulates EMT and distant metastasis. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.