Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma.

Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma.
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DOI:
10.18632/oncotarget.16709
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发表时间:
2017-07-04
期刊:
影响因子:
--
通讯作者:
Guo J
Guo J
中科院分区:
其他
文献类型:
--
作者:
Fu L;Chen Q;Yao T;Li T;Ying S;Hu Y;Guo J

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环状RNA (Circular RNA, circRNAs)是一类长期被忽视的非编码RNA,近年来被发现具有多种功能。然而,大多数环状rna在肝细胞癌(HCC)中的诊断价值和机制尚不清楚。在本研究中,我们发现hsa_circ_0005986在HCC中的表达水平明显低于癌旁非肿瘤组织(P < 0.001)。其在HCC细胞系、HepG2、SMMC7721、Huh7、MHCC97L、MHCC97H、HCCLM3中的表达水平显著低于人正常肝细胞系L02 (P < 0.001)。此外,hsa_circ_0005986低表达水平与慢性乙型肝炎家族史(P = 0.001)、肿瘤直径(P < 0.001)、微血管侵犯(P = 0.026)、巴塞罗那临床肝癌(BCLC)分期(P < 0.001)相关。进一步的实验表明hsa_circ_0005986和Notch1mRNA都是miR-129-5p的靶点,hsa_circ_0005986的下调释放了miR-129-5p,降低了Notch1mRNA的表达水平。更重要的是,hsa_circ_0005986下调通过促进G0/G1期向S期转变来加速细胞增殖。我们得出结论,hsa_circ_0005986在肿瘤发生过程中发挥了microRNA海绵的作用,可以作为HCC的一种新的生物标志物。
Circular RNAs (circRNAs), a class of long-time-ignored noncoding RNA, have been revealed as multifunctional RNAs in recent years. However, the diagnostic values and the mechanism of most circRNAs in hepatocellular carcinoma (HCC) remain unknown. In this study, we revealed that the expression level of hsa_circ_0005986 in HCC was significantly lower than that in adjacent non-tumorous tissues (P < 0.001). Its levels in HCC cell lines, HepG2, SMMC7721, Huh7, MHCC97L, MHCC97H, and HCCLM3 were significantly lower than those in human normal hepatic cell line L02 (P < 0.001). In addition, the low expression level of hsa_circ_0005986 was correlated with chronic hepatitis B family history (P = 0.001), tumor diameters (P < 0.001), microvascular invasion (P = 0.026), and Barcelona Clinic Liver Cancer (BCLC) stage (P < 0.001). Further experiments demonstrated that both hsa_circ_0005986 and Notch1mRNA were targets of miR-129-5p, and that hsa_circ_0005986 downregulation liberated miR-129-5p and decreased the expression level of Notch1mRNA. More importantly, hsa_circ_0005986 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that hsa_circ_0005986 function as microRNA sponge in tumorigenesis and can be used as a novel biomarker for HCC.
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