Circ_DCAF6 potentiates cell stemness and growth in breast cancer through GLI1-Hedgehog pathway

Circ_DCAF6 通过 GLI1-Hedgehog 通路增强乳腺癌细胞的干细胞特性和生长

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作者:Guolin Ye, Ruilin Pan, Leiwei Zhu, Dan Zhou

Abstract

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.

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