Long noncoding RNA CPS1-IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1.

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.

• Authors: Xiaobo Zhou, Yamin Rao, Qilin Sun, Yang Liu, Jun Chen, Wenbo Bu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 12 Pg. 22017-22027 (12 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 31111478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• CCN1 protein, human
• Cysteine-Rich Protein 61
• Nuclear Proteins
• RNA, Long Noncoding
• Transcription Factors
• SMARCA4 protein, human
• DNA Helicases

Topics

• Adult
• Cell Movement (genetics)
• Cysteine-Rich Protein 61 (genetics, metabolism)
• DNA Helicases (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Male
• Melanoma (genetics, metabolism, pathology)
• Middle Aged
• Neoplasm Invasiveness (genetics)
• Nuclear Proteins (genetics, metabolism)
• RNA, Long Noncoding (genetics)
• Skin Neoplasms (genetics, metabolism, pathology)
• Transcription Factors (genetics, metabolism)
• Melanoma, Cutaneous Malignant