Ji Yang, Yang Shikun, Yan Xueqi, Zhu Li, Yang Wenjie, Yang Xinchen, Yu Fei, Shi Longqing, Zhu Xi, Lu Yunjie, Zhang Chuanyong, Lu Hao, Zhang Feng
Key Laboratory of Liver Transplantation, Hepatobiliary/Liver Transplantation Center, Chinese Academy of Medical Sciences, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Cell Dev Biol. 2021 Nov 12;9:796686. doi: 10.3389/fcell.2021.796686. eCollection 2021.
Mounting evidence has demonstrated that circular RNAs have an important function in tumorigenesis and cancer evolvement. CircCRIM1 has been shown to be a poor prognostic element in multiple human malignancies. However, the clinical significance and mechanism of circCRIM1 in hepatocellular carcinoma (HCC) is still unclear. The present study confirmed the expression level of circCRIM1 using quantitative real-time PCR. In addition, circCRIM1 siRNA and overexpression vectors were used for transfection into LM3 or Huh7 cells to down- or up-regulate the expression of circCRIM1. and experiments were performed to explore the function of circCRIM1 in HCC. RNA pull-down, RNA immunoprecipitation, fluorescent hybridization, and luciferase reporter assays were conducted to confirm the relationship between miR-378a-3p and circCRIM1 or S-phase kinase-associated protein 2 (SKP2) in HCC. Then, circCRIM1 was up-regulated in HCC and its expression level was significantly associated with poor prognosis and clinicopathologic characteristics. CircCRIM1 enhanced the proliferation and angiogenesis of HCC cells and promoted xenograft growth . Moreover, circCRIM1 upregulated the expression of SKP2 by functioning as a sponge for miR-378a-3p. These findings suggest that circCRIM1 boosts the HCC progression via the miR-378-3p/SKP2 axis and may act as a crucial epigenetic therapeutic molecule target in HCC.
越来越多的证据表明，环状RNA在肿瘤发生和癌症进展中具有重要作用。CircCRIM1已被证明是多种人类恶性肿瘤中预后不良的因素。然而，circCRIM1在肝细胞癌（HCC）中的临床意义和机制仍不清楚。本研究通过定量实时PCR确定了circCRIM1的表达水平。此外，使用circCRIM1 siRNA和过表达载体转染LM3或Huh7细胞，以下调或上调circCRIM1的表达。并进行实验以探索circCRIM1在HCC中的功能。进行了RNA下拉、RNA免疫沉淀、荧光原位杂交和荧光素酶报告基因检测，以确认miR-378a-3p与HCC中circCRIM1或S期激酶相关蛋白2（SKP2）之间的关系。然后，circCRIM1在HCC中上调，其表达水平与不良预后和临床病理特征显著相关。CircCRIM1增强了HCC细胞的增殖和血管生成，并促进了异种移植瘤的生长。此外，circCRIM1通过作为miR-378a-3p的海绵发挥作用，上调了SKP2的表达。这些发现表明，circCRIM1通过miR-378-3p/SKP2轴促进HCC进展，可能是HCC中关键的表观遗传治疗分子靶点。
