A Novel ceRNA Regulatory Network Involving the Long Non-Coding Antisense RNA SPACA6P-AS, miR-125a and its mRNA Targets in Hepatocarcinoma Cells.
Int J Mol Sci
; 21(14)2020 Jul 17.
Article
en En
| MEDLINE
| ID: mdl-32709089
ABSTRACT
MicroRNAs (miRNA), and more recently long non-coding RNAs (lncRNA), are emerging as a driving force for hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death. In this work, we investigated a possible RNA regulatory network involving two oncosuppressive miRNAs, miR-125a and let-7e, and a long non-coding antisense RNA, SPACA6P-AS (SP-AS), all transcribed from the same locus, with SP-AS in the opposite direction and thus carrying complementary sequences to the miRNAs. In vitro experiments validated the binding of the miRNAs to SP-AS. Then, the boosting of either the miRNAs or SP-AS levels demonstrated their reciprocal inhibition. In addition, overexpression of SP-AS resulted in a reduced silencing activity of miR-125a and let-7e toward their key oncogenic targets, i.e., Lin28b, MMP11, SIRT7, Zbtb7a, Cyclin D1, CDC25B, HMGA2, that resulted significantly upregulated. Finally, the analysis of 374 HCC samples in comparison to 50 normal liver tissues showed an upregulation of SP-AS and a reverse expression of miR-125a, not observed for let-7e; consistently, miR-125a oncogenic targets were upregulated. Overall, the data depict a novel competing endogenous RNA (ceRNA) network, ceRNET, whereby miR-125a can regulate the expression of SP-AS, which in turn regulates the miRNA by competing with the binding to the mRNA targets. We speculate that the unbalancing of any network component may contribute to hepatocarcinogenesis.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ARN Mensajero
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Carcinoma Hepatocelular
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MicroARNs
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Redes Reguladoras de Genes
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ARN Largo no Codificante
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia