Long noncoding RNA CPS1‐IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1. Issue 12 (20th May 2019)

• Record Type: Journal Article
• Authors: Zhou, Xiaobo; Rao, Yamin; Sun, Qilin; Liu, Yang; Chen, Jun; Bu, Wenbo
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 12(2019:Dec.)
• Page Start: 22017
• Page End: 22027
• Publication Date: 2019-05-20
• Subjects: BRG1 -- CPS1‐IT1 -- Cyr61 -- melanoma -- metastasis; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28764
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : 1. CPS1‐IT1 is distinctly downregulated in human melanoma tissues, especially metastatic and advanced tissues, so is that in melanoma cell lines. 2. CPS1‐IT1 has a high potential to serve as an independent predictor for melanoma prognosis. 3. CPS1‐IT1 overexpression inhibits cell migration, invasion, epithelial–mesenchymal transition, and angiogenesis via a Cyr61‐mediated way in melanoma cells. 4. CPS1‐IT1 hampers Cyr61 expression through impairing the recruitment of BRG1‐guided SWI/SNF complex to Cyr61 promoter.