LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults; little is known about the contribution of non-coding RNAs (ncRNAs) to UM pathogenesis. Competitive endogenous RNA (ceRNA) networks based on RNA–RNA interactions regulate physiological and pathological processes. Th...

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Main Authors: Cristina Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Andrea Russo, Lidia Puzzo, Teresio Avitabile, Antonio Longo, Michele Reibaldi, Davide Barbagallo, Cinzia Di Pietro, Michele Purrello, Marco Ragusa
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/12/3867
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author Cristina Barbagallo
Rosario Caltabiano
Giuseppe Broggi
Andrea Russo
Lidia Puzzo
Teresio Avitabile
Antonio Longo
Michele Reibaldi
Davide Barbagallo
Cinzia Di Pietro
Michele Purrello
Marco Ragusa
author_facet Cristina Barbagallo
Rosario Caltabiano
Giuseppe Broggi
Andrea Russo
Lidia Puzzo
Teresio Avitabile
Antonio Longo
Michele Reibaldi
Davide Barbagallo
Cinzia Di Pietro
Michele Purrello
Marco Ragusa
author_sort Cristina Barbagallo
collection DOAJ
description Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults; little is known about the contribution of non-coding RNAs (ncRNAs) to UM pathogenesis. Competitive endogenous RNA (ceRNA) networks based on RNA–RNA interactions regulate physiological and pathological processes. Through a combined approach of in silico and experimental biology, we investigated the expression of a set of long non-coding RNAs (lncRNAs) in patient biopsies, identifying <i>LINC00518</i> as a potential oncogene in UM. The detection of <i>LINC00518</i> dysregulation associated with several in vitro functional assays allowed us to investigate its ceRNA regulatory network and shed light on its potential involvement in cancer-related processes, such as epithelial to mesenchymal transition (EMT) and CoCl<sub>2</sub>-induced hypoxia-like response. In vitro transient silencing of <i>LINC00518</i> impaired cell proliferation and migration, and affected mRNA expression of <i>LINGO2</i>, <i>NFIA</i>, <i>OTUD7B</i>, <i>SEC22C</i>, and <i>VAMP3</i>. A “miRNA sponge” and “miRNA protector” model have been hypothesized for <i>LINC00518</i>-induced regulation of mRNAs. In vitro inhibition of <i>MITF</i> suggested its role as a potential activator of <i>LINC00518</i> expression. Comprehensively, <i>LINC00518</i> may be considered a new oncogene in UM and a potential target for RNA-based therapeutic approaches.
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spelling doaj.art-fa8dea24684747d0951a8583ede7736e2023-11-21T01:55:31ZengMDPI AGCancers2072-66942020-12-011212386710.3390/cancers12123867LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based NetworkCristina Barbagallo0Rosario Caltabiano1Giuseppe Broggi2Andrea Russo3Lidia Puzzo4Teresio Avitabile5Antonio Longo6Michele Reibaldi7Davide Barbagallo8Cinzia Di Pietro9Michele Purrello10Marco Ragusa11Department of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, ItalyDepartment of Medical, Surgical Sciences and Advanced Technologies G.F, Ingrassia—Section of Anatomic Pathology, University of Catania, 95123 Catania, ItalyDepartment of Medical, Surgical Sciences and Advanced Technologies G.F, Ingrassia—Section of Anatomic Pathology, University of Catania, 95123 Catania, ItalyEye Clinic, University of Catania, 95123 Catania, ItalyDepartment of Medical, Surgical Sciences and Advanced Technologies G.F, Ingrassia—Section of Anatomic Pathology, University of Catania, 95123 Catania, ItalyEye Clinic, University of Catania, 95123 Catania, ItalyEye Clinic, University of Catania, 95123 Catania, ItalyEye Clinic, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, ItalyUveal melanoma (UM) is the most common primary intraocular malignant tumor in adults; little is known about the contribution of non-coding RNAs (ncRNAs) to UM pathogenesis. Competitive endogenous RNA (ceRNA) networks based on RNA–RNA interactions regulate physiological and pathological processes. Through a combined approach of in silico and experimental biology, we investigated the expression of a set of long non-coding RNAs (lncRNAs) in patient biopsies, identifying <i>LINC00518</i> as a potential oncogene in UM. The detection of <i>LINC00518</i> dysregulation associated with several in vitro functional assays allowed us to investigate its ceRNA regulatory network and shed light on its potential involvement in cancer-related processes, such as epithelial to mesenchymal transition (EMT) and CoCl<sub>2</sub>-induced hypoxia-like response. In vitro transient silencing of <i>LINC00518</i> impaired cell proliferation and migration, and affected mRNA expression of <i>LINGO2</i>, <i>NFIA</i>, <i>OTUD7B</i>, <i>SEC22C</i>, and <i>VAMP3</i>. A “miRNA sponge” and “miRNA protector” model have been hypothesized for <i>LINC00518</i>-induced regulation of mRNAs. In vitro inhibition of <i>MITF</i> suggested its role as a potential activator of <i>LINC00518</i> expression. Comprehensively, <i>LINC00518</i> may be considered a new oncogene in UM and a potential target for RNA-based therapeutic approaches.https://www.mdpi.com/2072-6694/12/12/3867UMlncRNAsmiRNA spongemiRNA protectorMITFceRNA network
spellingShingle Cristina Barbagallo
Rosario Caltabiano
Giuseppe Broggi
Andrea Russo
Lidia Puzzo
Teresio Avitabile
Antonio Longo
Michele Reibaldi
Davide Barbagallo
Cinzia Di Pietro
Michele Purrello
Marco Ragusa
LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
Cancers
UM
lncRNAs
miRNA sponge
miRNA protector
MITF
ceRNA network
title LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
title_full LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
title_fullStr LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
title_full_unstemmed LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
title_short LncRNA <i>LINC00518</i> Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network
title_sort lncrna i linc00518 i acts as an oncogene in uveal melanoma by regulating an rna based network
topic UM
lncRNAs
miRNA sponge
miRNA protector
MITF
ceRNA network
url https://www.mdpi.com/2072-6694/12/12/3867
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