Department of Hepatobiliary Surgical, First Hospital of Jiaxing, Jiaxing, China.
Cell Biochem Funct. 2019 Mar;37(2):84-92. doi: 10.1002/cbf.3375. Epub 2019 Feb 18.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death over the world. It is well studied that long noncoding RNA colon cancer-associated transcript-1 (CCAT1) played important roles in variety of cancers promoting cell proliferation and metastasis by acting as a competing endogenous RNA (ceRNA) of microRNAs. However, whether CCAT1 could regulate HCC by serving as a ceRNA of microRNA remains to be revealed. In this study, we demonstrated that CCAT1 was highly expressed in HCC tissues and remarkably associated with metastasis. With a bioinformatics prediction and functional assay validation, we found a binding site of miR-30c-2-3p on CCAT1, which was important for CCAT1 to promote cell proliferation. Interestingly, we further revealed a novel recognition site for miR-30c-2-3p on the 3'UTR of CCNE1 by mutative method, luciferase assay, and cell viability confirmation. In general, CCAT1 regulate the expression of CCNE1 by acting as a ceRNA to sponge miR-30c-2-3p in regulating the cell proliferation of HCC. These results suggest that CCAT1 may be a new therapy target for HCC in the future. SIGNIFICANCE OF THE STUDY: Our findings may broaden the understanding of the role of CCAT1 in tumorigenesis and may provide a new therapy target for HCC.
肝细胞癌 (HCC) 是全球癌症相关死亡的第二大主要原因。已有研究表明,长链非编码 RNA 结肠癌相关转录本-1 (CCAT1) 通过作为 microRNA 的竞争性内源 RNA (ceRNA) 在多种癌症中发挥重要作用,促进细胞增殖和转移。然而,CCAT1 是否可以通过作为 microRNA 的 ceRNA 来调节 HCC 仍有待揭示。在这项研究中,我们证明 CCAT1 在 HCC 组织中高度表达,并与转移显着相关。通过生物信息学预测和功能测定验证,我们发现了 miR-30c-2-3p 与 CCAT1 的结合位点,这对于 CCAT1 促进细胞增殖很重要。有趣的是,我们通过突变方法、荧光素酶测定和细胞活力验证进一步揭示了 miR-30c-2-3p 在 CCNE1 3'UTR 上的一个新识别位点。总的来说,CCAT1 通过作为 ceRNA 来海绵 miR-30c-2-3p 来调节 HCC 细胞的增殖,从而调节 CCNE1 的表达。这些结果表明,CCAT1 可能成为未来 HCC 的新治疗靶点。研究的意义:我们的发现可能拓宽了对 CCAT1 在肿瘤发生中的作用的理解,并为 HCC 提供了一个新的治疗靶点。