Reciprocal interplay of miR-497 and MALAT1 promotes tumourigenesis of adrenocortical cancer.
Endocr Relat Cancer
; 26(7): 677-688, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31085769
ABSTRACT
Adrenocortical carcinoma (ACC) has high recurrence rates and poor prognosis with limited response to conventional cancer therapy. Recent contributions of high-throughput transcriptomic profiling identified microRNA-497 (miR-497) as significantly underexpressed, while lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) as overexpressed in ACC. miR-497 is located in the chromosomal region 17p13.1, in which there is a high frequency of loss of heterozygosity in ACC. We aim to investigate the interaction of miR-497 and MALAT1 in ACC and its functional roles in the process of tumourigenesis. In this study, we demonstrated miR-497 post-transcriptionally repressed MALAT1 while MALAT1 also competes for miR-497 binding to its molecular target, EIF4E (eukaryotic translation initiation factor 4E). We showed that overexpression of miR-497 and silencing of MALAT1 suppressed cellular proliferation and induced cell cycle arrest through downregulation of EIF4E expression. Furthermore, MALAT1 directly binds to SFPQ (splicing factor proline and glutamine rich) protein, indicating its multifaceted roles in ACC pathophysiology. This is the first study to identify the feedback axis of miR-497-MALAT1/EIF4E in ACC tumourigenesis, providing novel insights into the molecular functions of noncoding RNAs in ACC.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Córtex Suprarrenal
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MicroRNAs
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RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Endocr Relat Cancer
Assunto da revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália