Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
J Cell Biochem. 2018 Aug;119(8):6391-6397. doi: 10.1002/jcb.26479. Epub 2018 May 9.
Cancer susceptibility candidate 2 (CASC2), a recently discovered long non-coding RNA (lncRNA), was confirmed to play numerous roles in several human cancers. However, the involvement and concrete mechanism of CASC2 in hepatocellular carcinoma (HCC) still need to be further elucidated. The relative expressions of CASC2 and miR-24-3p in HCC tissue and cell lines were determined by quantitative real-time PCR (qRT-PCR). The effects of CASC2 and miR-24-3p on HCC cells were further assessed via cell viability and apoptosis. In vivo tumorigenesis assay was performed to verify the inhibition effect of CASC2 on the tumor growth and further clarify the important role of miR-24-3p in this mechanism. Compared with the paired normal tissues, the relative expression of CASC2 significantly reduced in the HCC tissues, while miR-24-3p as determined by qRT-PCR obviously increased in the HCC tissues. This observation was also found in HCC cell lines. Meanwhile, the expression of CASC2 was negatively related to miR-24-3p expression in the HCC tissues (r = -0.804, P < 0.001). CASC2 could negatively regulate the expression of miR-24-3p in vitro. Moreover, CASC2 overexpression resulted in the growth inhibitory and apoptosis-inducing effects on HCC cells, but the up-regulation of miR-24-3p greatly eliminated the CASC2-induced effects. The tumorigenesis of HCC cells was restrained significantly by CASC2 overexpression as shown by decreased tumor volume and growth rate. However, miR-24-3p up-regulation rescued the inhibition of CASC2 on the tumor growth in tumor-bearing mice. LncRNA CASC2 inhibited the viability and induced the apoptosis of HCC cells through regulating miR-24-3p.
癌症易感性候选基因 2（CASC2）是一种新发现的长链非编码 RNA（lncRNA），已被证实参与多种人类癌症的发生。然而，CASC2 在肝细胞癌（HCC）中的作用及其具体机制仍需进一步阐明。采用实时定量 PCR（qRT-PCR）检测 HCC 组织和细胞系中 CASC2 和 miR-24-3p 的相对表达。通过细胞活力和凋亡进一步评估 CASC2 和 miR-24-3p 对 HCC 细胞的影响。进行体内肿瘤发生测定以验证 CASC2 对肿瘤生长的抑制作用，并进一步阐明 miR-24-3p 在该机制中的重要作用。与配对的正常组织相比，qRT-PCR 检测到 HCC 组织中 CASC2 的相对表达明显降低，而 miR-24-3p 的表达明显增加。在 HCC 细胞系中也观察到了这种情况。同时，HCC 组织中 CASC2 的表达与 miR-24-3p 的表达呈负相关（r=-0.804，P<0.001）。CASC2 可以在体外负调控 miR-24-3p 的表达。此外，CASC2 过表达对 HCC 细胞的生长抑制和凋亡诱导作用，但 miR-24-3p 的上调大大消除了 CASC2 诱导的作用。CASC2 过表达显著抑制 HCC 细胞的肿瘤发生，表现为肿瘤体积和生长速度降低。然而，miR-24-3p 的上调挽救了 CASC2 对荷瘤小鼠肿瘤生长的抑制作用。lncRNA CASC2 通过调节 miR-24-3p 抑制 HCC 细胞的活力并诱导其凋亡。
