Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Center for Specialty Strategy Research of Shanghai JiaoTong University China Hospital Development Institute, Shanghai, China.
Department of Pathology, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Center for Specialty Strategy Research of Shanghai JiaoTong University China Hospital Development Institute, Shanghai, China.
J Cell Physiol. 2019 Dec;234(12):22017-22027. doi: 10.1002/jcp.28764. Epub 2019 May 20.
Long noncoding RNA CPS1-IT1 is recently recognized as a tumor suppressor in several cancers. Here, we investigate the role of CPS1-IT1 in human melanoma. Presently, our study reveals the low expression of CPS1-IT1 in human melanoma tissues and cell lines, which is significantly associated with metastasis and tumor stage. Besides, the potential of CPS1-IT1 as a prognosis-predictor is strongly indicated. Functionally, CPS1-IT1 overexpression inhibits cell migration, invasion, epithelial-mesenchymal transition, and angiogenesis in melanoma cells. CYR61, an angiogenic factor that participates in tumor metastasis as well as a recognized oncogene in melanoma, is shown to be confined under CPS1-IT1 overexpression in melanoma cells. Furthermore, enforced expression of Cyr61 in CPS1-IT1-silenced melanoma cells dramatically normalized the protein level of Cyr61 and that of its downstream targets vascular endothelial growth factor and matrix metalloproteinase-9, as well as the repressive effect of CPS1-IT1 overexpression on melanoma cell metastasis. BRG1, a core component of SWI/SNF complex, is implied to interact with both CPS1-IT1 and Cyr61 in melanoma cells. Moreover, CPS1-IT1 negatively regulates Cyr61 expression by blocking the binding of BRG1 to Cyr61 promoter. Jointly, CPS1-IT1 controls melanoma metastasis through impairing Cyr61 expression via competitively binding with BRG1, uncovering a novel potential therapeutic and prognostic biomarker for patients with melanoma.
长链非编码 RNA CPS1-IT1 最近被认为是几种癌症中的肿瘤抑制因子。在这里，我们研究了 CPS1-IT1 在人类黑色素瘤中的作用。目前，我们的研究揭示了 CPS1-IT1 在人类黑色素瘤组织和细胞系中的低表达，这与转移和肿瘤分期显著相关。此外，强烈表明 CPS1-IT1 具有作为预后预测因子的潜力。功能上，CPS1-IT1 的过表达抑制黑色素瘤细胞的迁移、侵袭、上皮间质转化和血管生成。Cyr61 是一种参与肿瘤转移的血管生成因子，也是黑色素瘤中的公认癌基因，在黑色素瘤细胞中被证明受到 CPS1-IT1 过表达的限制。此外，在 CPS1-IT1 沉默的黑色素瘤细胞中强制表达 Cyr61，可显著使 Cyr61 及其下游靶标血管内皮生长因子和基质金属蛋白酶-9 的蛋白水平正常化，并使 CPS1-IT1 过表达对黑色素瘤细胞转移的抑制作用正常化。BRG1 是 SWI/SNF 复合物的核心组成部分，暗示其在黑色素瘤细胞中与 CPS1-IT1 和 Cyr61 相互作用。此外，CPS1-IT1 通过阻止 BRG1 与 Cyr61 启动子结合来负调控 Cyr61 表达。总之，CPS1-IT1 通过与 BRG1 竞争结合来抑制 Cyr61 表达，从而控制黑色素瘤转移，揭示了一种针对黑色素瘤患者的新的潜在治疗和预后生物标志物。
