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J Dig Dis ; 23(7): 376-387, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35844201

RESUMEN

OBJECTIVES: Circular RNAs (circRNAs) play pivotal roles in malignancies including gastric cancer (GC). We aimed to investigate the biological function and regulatory mechanism of circ_0006089 in GC. METHODS: Circ_0006089, microRNA (miR)-143-3p, and polypyrimidine tract-binding protein 3 (PTBP3) expressions were measured via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in GC cell lines. Cell proliferative capacity was determined by colony formation and CCK-8 assays. Flow cytometry was employed for measuring cell apoptosis. Cell invasion and migration were measured via transwell and wound-healing assays. Western blot analysis was utilized for detecting protein expressions of E-cadherin, N-cadherin, vimentin, PTBP3, PI3K, p-PI3K, AKT, and p-AKT. Dual-reporter luciferase analysis was conducted to confirm the association between miR-143-3p and circ_0006089 or PTBP3. The role of circ_0006089 in vivo was detected via establishing a mice xenograft model. RESULTS: Circ_0006089 expression was increased in GC. Circ_0006089 downregulation suppressed the proliferation and metastasis and induced apoptosis of GC cells, which was counteracted by miR-143-3p inhibition or PTBP3 overexpression. In addition, circ_0006089 overexpression could promote GC progression. MiR-143-3p specially bound to circ_0006089 and PTBP3 was targeted by miR-143-3p. Moreover, circ_0006089 could regulate PTBP3 expression and the PI3K/AKT pathway by sponging miR-143-3p. Circ_0006089 knockdown also suppressed tumor growth. CONCLUSION: Circ_0006089 regulated miR-143-3p/PTBP3/PI3K/AKT pathway to facilitate GC progression.


Asunto(s)
ARN Circular/metabolismo , Transducción de Señal , Neoplasias Gástricas , Animales , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sincalida/genética , Sincalida/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Vimentina/genética , Vimentina/metabolismo
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