The circular RNA circSLC7A11 functions as a mir-330-3p sponge to accelerate hepatocellular carcinoma progression by regulating cyclin-dependent kinase 1 expression.

The circular RNA circSLC7A11 functions as a mir-330-3p sponge to accelerate hepatocellular carcinoma progression by regulating cyclin-dependent kinase 1 expression.
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环状RNA circSLC7A11作为mir-330-3p海绵发挥作用,通过调节细胞周期蛋白依赖性激酶1的表达来加速肝细胞癌的进展

DOI:
10.1186/s12935-021-02351-7
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发表时间:
2021-11-29
影响因子:
5.8
通讯作者:
Wang W
Wang W
中科院分区:
医学2区
文献类型:
--
作者:
Huang Y;Ge W;Ding Y;Zhang L;Zhou J;Kong Y;Cui B;Gao B;Qian X;Wang W

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环状RNA(circRNA)是内源性非编码RNA,与发育、稳态维持和病理反应等多种生物学过程相关。越来越多的证据表明非编码RNA参与了癌症的进展,特别是circRNA的作用引起了广泛的关注。然而,circRNA在肝细胞癌(HCC)中的表达模式和功能仍然知之甚少。进行CircRNA测序以筛选HCC中差异表达的circRNA。采用北方印迹、实时定量聚合酶链反应、核质分级和荧光原位杂交等方法检测circSLC 7 A11在HCC组织和细胞中的表达和定位。在培养的HCC细胞系中改变了circSLC 7A 11表达水平,以使用几种基于细胞的测定来探索circSLC 7A 11的表达与这些细胞的恶性行为之间的关联。将修饰的细胞植入免疫活性的裸鼠中以评估体内肿瘤生长和转移。我们应用生物信息学方法、RNA pulldown、RNA免疫沉淀和荧光素酶报告基因分析来探讨circSLC 7A 11在HCC中的作用机制。CircSLC 7A 11(hsa_circ_0070975)在HCC组织和细胞中是保守的并且显著过表达。显示circSLC 7A 11高表达的HCC患者具有更差的预后。我们的体外和体内实验表明,circSLC 7A 11通过circSLC 7A 11/miR-330- 3 p/CDK 1轴显著加速HCC进展和转移。circSLC 7A 11通过circSLC 7A 11/miR-330- 3 p/CDK 1轴加速HCC进展和转移,表明circSLC 7A 11是HCC治疗的潜在新型诊断和治疗靶标。在线版本包含补充材料,可通过10.1186/s12935-021-02351-7获得。
Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood. CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC. CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis. The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment. The online version contains supplementary material available at 10.1186/s12935-021-02351-7.
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