Circular RNA circUBXN7 represses cell growth and invasion by sponging miR-1247-3p to enhance B4GALT3 expression in bladder cancer.

Circular RNA circUBXN7 represses cell growth and invasion by sponging miR-1247-3p to enhance B4GALT3 expression in bladder cancer.
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环状RNA circUBxN7通过海绵miR-1247-3p增强膀胱癌中B4GALT3的表达来抑制细胞生长和侵袭

DOI:
10.18632/aging.101573
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发表时间:
2018-10-12
期刊:
Aging
影响因子:
--
通讯作者:
Huang J
Huang J
中科院分区:
其他
文献类型:
--
作者:
Liu H;Chen D;Bi J;Han J;Yang M;Dong W;Lin T;Huang J

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环状RNA(CircRNAs)最近被证实参与了不同的病理过程,包括癌症的进展。然而,大多数CircRNAs在膀胱癌中的作用和确切的作用机制尚未阐明。在这里,我们发现了一种新的环状RNA,命名为CircUBXN7,与匹配的非肿瘤组织相比,它在BC组织中显著下调。重要的是,我们发现UBXN7的低表达与BC患者的病理分期、分级和预后不良有关。功能实验表明,该基因在体外能显著抑制肿瘤的增殖、迁移和侵袭,并能抑制体内肿瘤的生长。UBXN7可直接与miR-1247-3p结合,逆转miR-1247-3p的致癌效应。此外,B4GALT3被预测并确认为miR-1247-3p的靶标。救援实验表明,UBXN7可阻断miR-1247-3p对B4GALT3表达的抑制作用。最后,沉默B4GALT3促进了BC细胞的增殖和侵袭,并部分取消了大约UBXN7对肿瘤的抑制作用。综上所述,我们的研究表明,CircUBXN7作为miR-1247-3p的竞争内源RNA,上调B4GALT3的表达,从而抑制BC的细胞存活和侵袭。UBXN7-miR-1247-3p-B4GALT3调控网络可能为BC的基因治疗策略提供新的视角。
Circular RNAs (circRNAs) have recently been confirmed to participate in different pathological processes, including cancer progression. However, the role and precise mechanism of action of the majority of circRNAs have not been elucidated in bladder cancer (BC). Here, we identified a novel circular RNA, termed circUBXN7, which was significantly downregulated in BC tissues compared with matched nontumor tissues. Importantly, we found that decreased circUBXN7 expression was associated with pathological stage, grade and poor prognosis of BC patients. Functional experiments showed that circUBXN7 overexpression dramatically inhibited proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Mechanistically, circUBXN7 could directly bind to miR-1247-3p and reverse the oncogenic effects induced by miR-1247-3p. Furthermore, B4GALT3 was predicted and confirmed to be a target of miR-1247-3p. Rescue experiments demonstrated that circUBXN7 abrogated miR-1247-3p-mediated inhibition of B4GALT3 expression. Finally, silencing of B4GALT3 promoted proliferation and invasion of BC cells; and partially abolished the tumor suppressive effects caused by circUBXN7. Taken together, our study revealed that circUBXN7 serves as a competitive endogenous RNA of miR-1247-3p to elevate B4GALT3 expression, consequently inhibiting cell viability and invasion in BC. The circUBXN7-miR-1247-3p-B4GALT3 regulatory network may provide a new perspective for gene-based treatment strategies for BC.
N6-甲基腺苷驱动的环状 RNA 的广泛翻译。
DOI: 10.1038/cr.2017.31
发表时间: 2017-05
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影响因子: 44.1
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