circ-BIRC6, a circular RNA, promotes hepatocellular carcinoma progression by targeting the miR-3918/Bcl2 axis
circ-BIRC6, a circular RNA, promotes hepatocellular carcinoma progression by targeting the miR-3918/Bcl2 axis
复制标题
circ-BIRC6 是一种环状 RNA，通过靶向 miR-3918/Bcl2 轴促进肝细胞癌进展
DOI：
10.1080/15384101.2019.1601477
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发表时间：
2019-05-03
期刊：
影响因子：
4.3
通讯作者：
Li, Jie
中科院分区：
文献类型：
--
作者：
Yang, Guangsheng;Wang, Xin;Li, Jie
环状RNA （circ）是一种特殊类型的内源性RNA，由共价闭环结构组成，没有5到3极性和聚腺苷化的尾部。越来越多的证据表明，环状rna在人类癌症的发生和发展中发挥着重要作用。然而，环状rna在肝细胞癌（HCC）进展中的作用在很大程度上是未知的。本研究利用高通量测序技术鉴定HCC患者组织和细胞系中异常表达的环状rna，解决了这一问题。我们发现环杆状病毒含IAP重复序列（BIRC）6在HCC组织样本和细胞中上调；这与HCC患者的总生存率相关。circ-BIRC6敲低可降低HCC细胞的增殖、迁移和侵袭，并促进其凋亡。此外，circ-BIRC6过表达负向调节microRNA miR-3918的表达，miR-3918被鉴定为B细胞淋巴瘤（Bcl）的抑制剂2。circ-BIRC6缺失的肿瘤抑制作用通过抑制miR-3918而被消除。这些结果表明，circ-BIRC6作为一种竞争性内源性RNA，通过海绵miR-3918调节Bcl2的表达，可能作为HCC治疗的预后生物标志物和治疗靶点。
Circular (circ)RNA is a special type of endogenous RNA consisting of a covalently closed loop structure without 5 to 3 polarity and a polyadenylated tail. Accumulating evidence suggests that circRNAs play important roles in the development and progression of human cancers. However, the role of circRNAs in the progression of hepatocellular carcinoma (HCC) is largely unknown. This was addressed in the present study using high-throughput sequencing to identify aberrantly expressed circRNAs in HCC patient tissue and cell lines. We found that circ-baculoviral IAP repeat-containing (BIRC)6 was upregulated in HCC tissue samples and cells; this was associated with the overall survival of HCC patients. circ-BIRC6 knockdown reduced HCC cell proliferation, migration, and invasion and enhanced their apoptosis. Additionally, circ-BIRC6 overexpression negatively regulated the expression of microRNA miR-3918, which was identified as an inhibitor of B cell lymphoma (Bcl)2. The tumor-suppressive effect of circ-BIRC6 deletion was abrogated by inhibiting miR-3918. These results indicate that circ-BIRC6 functions as a competing endogenous RNA that regulates Bcl2 expression by sponging miR-3918, and may serve as a prognostic biomarker and therapeutic target for the treatment of HCC.