Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We became interested in a lncRNA, steroid receptor RNA activator (SRA), because it is the first lncRNA also encoding a conserved protein, SRAP, and it regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, epithelial-mesenchymal transformation (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 results showed that SRA knockdown decreased B16 cell and A375 cell proliferation and inhibited B16 cell migration significantly. Transwell analysis revealed that CCL21-mediated invasion was abolished in SRA-deficient B16 cells. In parallel, p38 dephosphorylation and reciprocal phosphorylation of B-Raf and mitogen-activated protein kinase kinase 1/2 were present in B16–SRA inhibited cells. The induction of EMT markers, β-catenin and N-cadherin, by CCL21 was reduced in B16–SRA inhibited cells, suggesting that SRA promotes the EMT process. In vivo experimental metastasis showed that B16–SRA inhibited cells formed significantly fewer tumor nodules in the lungs grossly and microscopically. In summary, our results showed that SRA expression is increased in melanoma tissue and that SRA mediates p38 activation, cell invasion, and proliferation and regulates EMT and distant metastasis.

即使使用当前的检查点抑制剂，黑色素瘤转移也预示着不良预后。长非编码RNA（lncRNA）调节包括黑素瘤在内的多种癌症的动态转移。我们对lncRNA，类固醇受体RNA激活剂（SRA）产生了兴趣，因为它是第一个也编码保守蛋白SRAP的lncRNA，并且它调节前列腺癌和乳腺癌的进展。我们调查了SRA如何通过RNA干扰介导黑色素瘤的增殖，迁移，侵袭，上皮-间质转化（EMT）和转移。通过免疫荧光和PCR测定SRAP在黑素瘤组织以及人和小鼠B16黑素瘤细胞中的表达。结果表明，SRA抑制降低B16细胞和A375细胞的增殖，并显着抑制B16细胞迁移。Transwell分析表明，在SRA缺陷型B16细胞中CCL21介导的侵袭被消除。同时，在B16-SRA抑制的细胞中，B-Raf和有丝分裂原活化的蛋白激酶激酶1/2的p38脱磷酸化和相互磷酸化。在B16–SRA抑制的细胞中，CCL21对EMT标记物β-catenin和N-cadherin的诱导作用降低，表明SRA促进了EMT过程。体内实验转移表明，B16–SRA抑制的细胞在肉眼和显微镜下在肺中形成的肿瘤结节明显减少。总之，我们的结果表明SRA在黑色素瘤组织中表达增加，并且SRA介导p38激活，细胞侵袭和增殖并调节EMT和远处转移。在B16-SRA抑制的细胞中，B-Raf和有丝分裂原活化的蛋白激酶激酶1/2存在p38的去磷酸化和相互磷酸化。在B16–SRA抑制的细胞中，CCL21对EMT标记物β-catenin和N-cadherin的诱导作用降低，表明SRA促进了EMT过程。体内实验转移表明，B16–SRA抑制的细胞在肉眼和显微镜下在肺中形成的肿瘤结节明显减少。总之，我们的结果表明SRA在黑色素瘤组织中表达增加，并且SRA介导p38激活，细胞侵袭和增殖并调节EMT和远处转移。在B16-SRA抑制的细胞中，B-Raf和有丝分裂原活化的蛋白激酶激酶1/2存在p38的去磷酸化和相互磷酸化。在B16–SRA抑制的细胞中，CCL21对EMT标记物β-catenin和N-cadherin的诱导作用降低，表明SRA促进了EMT过程。体内实验转移表明，B16–SRA抑制的细胞在肉眼和显微镜下在肺中形成的肿瘤结节明显减少。总之，我们的结果表明SRA在黑色素瘤组织中表达增加，并且SRA介导p38激活，细胞侵袭和增殖并调节EMT和远处转移。CCL21的作用在B16–SRA抑制的细胞中减少，表明SRA促进了EMT过程。体内实验转移表明，B16–SRA抑制的细胞在肉眼和显微镜下在肺中形成的肿瘤结节明显减少。总之，我们的结果表明SRA在黑色素瘤组织中表达增加，并且SRA介导p38激活，细胞侵袭和增殖并调节EMT和远处转移。CCL21的作用在B16–SRA抑制的细胞中减少，表明SRA促进了EMT过程。体内实验转移表明，B16–SRA抑制的细胞在肉眼和显微镜下在肺中形成的肿瘤结节明显减少。总之，我们的结果表明SRA在黑色素瘤组织中表达增加，并且SRA介导p38激活，细胞侵袭和增殖并调节EMT和远处转移。