MicroRNA-143-3p targets pyruvate carboxylase expression and controls proliferation and migration of MDA-MB-231â¯cells.
Arch Biochem Biophys
; 677: 108169, 2019 11 30.
Article
em En
| MEDLINE
| ID: mdl-31697914
ABSTRACT
Pyruvate carboxylase (PC) is a biotin-containing enzyme that converts pyruvate to oxaloacetate. We have previously shown that PC is overexpressed in highly invasive cancer cell lines where it supports biosynthesis during rapid cell growth. Here, we show that miR-143-3p suppresses the expression of PC in MDA-MB-231â¯cells by targeting its conserved binding site in the 3'-untranslated region (UTR) of human PC mRNA. Incorporation of the PC 3'UTR into a luciferase reporter gene inhibited expression of luciferase by 50% while mutation of the miR-143-3p binding site abrogated this inhibitory effect in MDA-MB-231â¯cells but not in low aggressive MCF-7â¯cell line. Transfection of miR-143-3p mimic or overexpression of miR-143-3p using tetracycline-inducible system in MDA-MB-231â¯cells down-regulated expression of both endogenous PC mRNA and protein by 40% and 50% respectively, confirming the regulatory role of miR-143-3p in PC expression. Induction of miR-143-3p expression at low and high levels lowered proliferation, metabolic activity and migration of MDA-MB-231â¯cells, in a dose-dependent manner. Re-expression of PC in MDA-MB-231â¯cells which were induced to express miR-143-3p partially restored migration but not proliferation, indicating that miR-143-3p regulates proliferation and migration through multiple pathways.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piruvato Carboxilase
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Regulação Neoplásica da Expressão Gênica
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Movimento Celular
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MicroRNAs
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Proliferação de Células
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article