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Exp Mol Pathol ; 116: 104492, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32668286

RESUMO

Circular RNAs (circRNAs) are extensively revealed as a malignant activator or suppressor in multiple pathological processes including cancer cell stemness and growth. However, the association of circ_DCAF6 with breast cancer (BC) cell growth and stemness has not been well depicted. In this research, qRT-PCR clarified the high level of circ_DCAF6 in BC cells. In functional aspects, BC cells presented suppressed proliferation and stemness in the absence of circ_DCAF6. The potential correlation of circ_DCAF6 with Hedgehog (Hh) pathway was unveiled utilizing its specific inhibitor or agonist in qRT-PCR and functional assays. Circ_DCAF6 positively mediated the expression of GLI1 and its facilitating impacts on BC cell proliferation and stemness required the participation of GLI1-dependent Hh signaling pathway. In depth, circ_DCAF6 post-transcriptionally upregulated GLI1 expression through sequestering miR-616-3p. Rescue experiments verified that the suppressive influence of circ_DCAF6 depletion or miR-616-3p upregulation on BC progression was reversed by GLI1 upregulation. In summary, a probable contribution of circ_DCAF6 to BC cell growth and stemness was elaborated. Circ_DCAF6 assisted in Hh signal pathway activation via the up-regulation of GLI1 by sponging miR-616-3p, generating new thoughts on future direction of antagonizing BC tumorigenesis and stem-like property.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Proteína GLI1 em Dedos de Zinco/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Hedgehog/genética , Humanos , Células MCF-7 , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/genética
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