ELF1-mediated LUCAT1 promotes choroidal melanoma by modulating RBX1 expression.

Abstract

Long noncoding RNAs (lncRNAs) are essential regulators of gene expression and biological behaviors. However, the contribution of lncRNA LUCAT1 to choroidal melanoma (CM) remains unexplored. Here, we examined the expression of LUCAT1 in CM cells by qRT-PCR and investigated its biological effects by cell counting kit-8, EdU, TUNEL, transwell assays, and Western blot. Bioinformatics tools were applied to find RNA candidates for further study. Moreover, mechanistic experiments including RNA immunoprecipitation assay, pull-down assay, and luciferase reporter assay confirmed the relation or interaction among the indicated molecules. Here, we reported ELF1 as the transcription activator of LUCAT1. Functionally, elevated expression of LUCAT1 positively regulated CM cell proliferation, metastasis, and epithelial-mesenchymal transition process. In addition, we verified the competing endogenous RNA (ceRNA) hypothesis of LUCAT1 and confirmed LUCAT1 modulates CM progression by modulating miR-514a/b-3p/RBX1 axis. Meanwhile, miR-514a/b-3p was suggested to repress CM progression, whereas RBX1 was unmasked to aggravate CM development. Of note, RBX1 overexpression rescued the inhibitory effect of LUCAT1 silence on the biological processes of CM cells. Altogether, this study unveiled the modulation axis ELF1/LUCAT1/miR-514a/b-3p/RBX1 and evidenced LUCAT1 as a promoter in CM for the first time, providing a novel insight into future treatment of CM.

• Authors: Lina Wang, Dongrun Tang, Tong Wu, Fengyuan Sun
• Journal: Cancer medicine (Cancer Med) Vol. 9 Issue 6 Pg. 2160-2170 (03 2020) ISSN: 2045-7634 [Electronic] United States
• PMID: 31968402 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Carrier Proteins
• ELF1 protein, human
• MIRN514 microRNA, human
• MicroRNAs
• Nuclear Proteins
• RBX1 protein, human
• RNA, Long Noncoding
• Transcription Factors
• long non-coding RNA LUCAT1, human

Topics

• Animals
• Carcinogenesis (genetics)
• Carrier Proteins (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Choroid Neoplasms (genetics, pathology)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Melanoma (genetics, pathology)
• Mice
• MicroRNAs (metabolism)
• Nuclear Proteins (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Transcription Factors (metabolism)
• Transcriptional Activation
• Xenograft Model Antitumor Assays