Zhou Yitong, Liu Kai, Liu Yahui, Tan Ludong
Department of Surgery, Changchun Medical College, Changchun, Jilin, China.
Department of Hepatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
J Cell Biochem. 2019 May;120(5):7147-7153. doi: 10.1002/jcb.27988. Epub 2018 Nov 26.
Hepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third-most common cause of cancer-related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA-34a (miR-34a) in HCC. In HCC tissues and cells, the expression levels of miR-34a were analyzed by quantitative real-time polymerase chain reaction. The association between the level of miR-34a and hexokinase (HK)-1 was also investigated via luciferase reporter assay. Cell viability and proliferation were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. To assess whether miR-34a can limit tumor growth in vivo, animal models and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used for examining the role of miR-34a on the development of HCC and cell apoptosis. The expression level of miR-34a was reduced in HCC samples and cells. The expression of miR-34a was associated with the viability and proliferation capacity of HCC cells, and miR-34a could inhibit HCC cells proliferation by inhibiting HK1. In the mouse model of HCC, volumes and weight of the tumors were significantly decreased by transfection with miR-34a mimic compared with the control group. Furthermore, miR-34a mimics could induce apoptosis in a greater proportion of cells compared with the control group. Taken together, the data may provide some novel insights into the molecular mechanism of miR-34a and HK1 in the progression of HCC. Thus, miR-34a/HK1 axis might be a novel promising therapeutic target for treating HCC.
肝细胞癌（HCC）是肝脏原发性癌症中常见的类型，也是全球癌症相关死亡的第三大常见原因。然而，HCC进展中的分子机制仍不清楚。本研究旨在探讨微小RNA-34a（miR-34a）在HCC中的表达及功能。在HCC组织和细胞中，通过定量实时聚合酶链反应分析miR-34a的表达水平。还通过荧光素酶报告基因检测法研究了miR-34a水平与己糖激酶（HK）-1之间的关联。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐检测法和流式细胞术检测细胞活力和增殖。为评估miR-34a是否能在体内限制肿瘤生长，使用动物模型和末端脱氧核苷酸转移酶dUTP缺口末端标记检测法来研究miR-34a在HCC发展和细胞凋亡中的作用。HCC样本和细胞中miR-34a的表达水平降低。miR-34a的表达与HCC细胞的活力和增殖能力相关，并且miR-34a可通过抑制HK1来抑制HCC细胞增殖。在HCC小鼠模型中，与对照组相比，转染miR-34a模拟物后肿瘤体积和重量显著减小。此外，与对照组相比，miR-34a模拟物可诱导更大比例的细胞凋亡。综上所述，这些数据可能为miR-34a和HK1在HCC进展中的分子机制提供一些新见解。因此，miR-34a/HK1轴可能是治疗HCC的一个新的有前景的治疗靶点。
