Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Dig Liver Dis. 2019 May;51(5):703-711. doi: 10.1016/j.dld.2018.09.021. Epub 2018 Sep 28.
Increasing evidence indicates that aberrant micro (mi)RNA-448 expression plays a critical role in the progression of several human cancers. However, the function of miRNA-448 in hepatocellular carcinoma (HCC) has not been fully investigated.
miRNA-448 expression levels in HCC tissues, adjacent non-cancerous tissues (ANTs), and HCC cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HCC cells were treated with a miRNA-448 mimic or inhibitor, followed by cell viability measurements with the CCK-8 assay. Venn diagram analysis predicted, and dual luciferase reporter assays verified, the target gene of miRNA-448. Expression of the target gene was detected by qRT-PCR and immunohistochemistry. Growth of miRNA-448- or target gene-expressing HCC xenograft tumors in nude mice was measured.
miRNA-448 was expressed at a lower level in HCC tissues than ANTs, and correlated with a larger tumor size, incomplete tumor encapsulation, and advanced Barcelona Clinic Liver Cancer stage. miRNA-448 inhibited HCC cell growth. The downstream target of miRNA-448 was BCL-2, which was highly expressed in HCC tissues and its mRNA level was negatively correlated with miRNA-448 expression. In vivo, BCL-2 attenuated the tumor inhibiting effect of miRNA-448.
miRNA-448 functions as a tumor suppressor by targeting BCL-2 in HCC.
越来越多的证据表明，异常表达的 micro (mi)RNA-448 在几种人类癌症的进展中起着关键作用。然而，miRNA-448 在肝细胞癌 (HCC) 中的功能尚未被充分研究。
通过实时定量聚合酶链反应 (qRT-PCR) 检测 HCC 组织、相邻非癌组织 (ANTs) 和 HCC 细胞系中的 miRNA-448 表达水平。用 miRNA-448 模拟物或抑制剂处理 HCC 细胞，然后用 CCK-8 测定法测量细胞活力。Venn 图分析预测，双荧光素酶报告基因检测验证了 miRNA-448 的靶基因。通过 qRT-PCR 和免疫组织化学检测靶基因的表达。在裸鼠中测量 miRNA-448 或靶基因表达的 HCC 异种移植肿瘤的生长。
miRNA-448 在 HCC 组织中的表达水平低于 ANTs，与肿瘤体积较大、肿瘤包膜不完整和巴塞罗那临床肝癌分期较晚相关。miRNA-448 抑制 HCC 细胞生长。miRNA-448 的下游靶基因是 BCL-2，它在 HCC 组织中高表达，其 mRNA 水平与 miRNA-448 表达呈负相关。在体内，BCL-2 减弱了 miRNA-448 的抑瘤作用。
miRNA-448 通过靶向 BCL-2 在 HCC 中发挥肿瘤抑制作用。
