College of Biotechnology, Guilin Medical University, Guilin, China.
College of Stomatology, Guangxi Medical University, Nanning, China.
J Cell Mol Med. 2020 Oct;24(20):12008-12019. doi: 10.1111/jcmm.15829. Epub 2020 Sep 8.
The role of the LMNA gene in the development and progression of hepatocellular carcinoma (HCC) and the associated molecular mechanism is not yet clear. Therefore, the purpose of this study was to evaluate the relationship between LMNA and HCC. LMNA gene expression in normal tissues and corresponding tumours was evaluated and the Kaplan-Meier survival analysis was performed. Next, the LMNA gene was knocked out in the 293T and HepG2 cell lines using the CRISPR/Cas9 technique. Subsequently, the proliferation, migration and colony formation rate of the two LMNA knockout cell lines were analysed. Finally, the molecular mechanism affecting the tumorigenesis due to the loss of the LMNA gene was evaluated. The results showed that the LMNA gene was abnormally expressed in many tumours, and the survival rate of the HCC patients with a high expression of the LMNA gene was significantly reduced compared with the rate in patients with a low LMNA expression. The knockout of the LMNA gene in the HCC cell line HepG2 resulted in a decreased tumorigenicity, up-regulation of the P16 expression and down-regulation of the CDK1 expression. These findings suggested that LMNA might function as an oncogene in HCC and provided a potential new target for the diagnosis and treatment of HCC.
LMNA 基因在肝细胞癌（HCC）的发生发展及相关分子机制中的作用尚不清楚。因此，本研究旨在探讨 LMNA 与 HCC 的关系。评估了正常组织和相应肿瘤中 LMNA 基因的表达，并进行了 Kaplan-Meier 生存分析。接下来，使用 CRISPR/Cas9 技术敲除 293T 和 HepG2 细胞系中的 LMNA 基因。然后分析了这两条 LMNA 敲除细胞系的增殖、迁移和集落形成率。最后，评估了由于 LMNA 基因缺失而影响肿瘤发生的分子机制。结果表明，LMNA 基因在多种肿瘤中异常表达，且高表达 LMNA 基因的 HCC 患者的生存率明显低于低表达 LMNA 的患者。在 HCC 细胞系 HepG2 中敲除 LMNA 基因导致肿瘤发生能力降低，P16 表达上调，CDK1 表达下调。这些发现提示 LMNA 可能在 HCC 中作为癌基因发挥作用，并为 HCC 的诊断和治疗提供了一个新的潜在靶点。
