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 LINC00518 as a potential oncogene in UM. The detection of LINC00518 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 CoCl2‐induced hypoxia‐like response. In vitro transient silencing of LINC00518 impaired cell proliferation and migration, and affected mRNA expression of LINGO2, NFIA, OTUD7B, SEC22C, and VAMP3. A “miRNA sponge” and “miRNA protector” model have been hypothesized for LINC00518‐induced regulation of mRNAs. In vitro inhibition of MITF suggested its role as a potential activator of LINC00518 expression. Comprehensively, LINC00518 may be considered a new oncogene in UM and a potential target for RNA‐based therapeutic approaches.

Lncrna Linc00518 acts as an oncogene in uveal melanoma by regulating an RNA‐based network

Barbagallo C.;Caltabiano R.;Broggi G.;Russo A.;Puzzo L.;Avitabile T.;Longo A.;Reibaldi M.;Barbagallo D.;Di Pietro C.;Purrello M.;Ragusa M.
2020-01-01

Abstract

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 LINC00518 as a potential oncogene in UM. The detection of LINC00518 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 CoCl2‐induced hypoxia‐like response. In vitro transient silencing of LINC00518 impaired cell proliferation and migration, and affected mRNA expression of LINGO2, NFIA, OTUD7B, SEC22C, and VAMP3. A “miRNA sponge” and “miRNA protector” model have been hypothesized for LINC00518‐induced regulation of mRNAs. In vitro inhibition of MITF suggested its role as a potential activator of LINC00518 expression. Comprehensively, LINC00518 may be considered a new oncogene in UM and a potential target for RNA‐based therapeutic approaches.
2020
CeRNA network
EMT
Hypoxia
LncRNAs
Migration
MiRNA protector
MiRNA sponge
MITF
RNA–RNA interactions
UM
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/494757
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