Li Hua, Shen Shen, Chen Xiaolong, Ren Zhigang, Li Zhiqin, Yu Zujiang
1Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, 1# Jianshe East Road, Zhengzhou, 450052 China.
2Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Cancer Cell Int. 2019 Jul 31;19:205. doi: 10.1186/s12935-019-0923-x. eCollection 2019.
Kinesin family member 26B (KIF26B) is unveiled acted as important role in many solid tumors, however, the function of KIF26B in hepatocellular carcinoma (HCC) is unclear.
The expression of KIF26B in HCC tissues and cell lines were measured with immunochemistry, real-time PCR and western blotting. The correlation between KIF26B expression and clinicopathological characteristics were analyzed by SPSS19.0. Functional experiments of KIF26B was conducted by CCK-8, transwell, EDU, colony formation in vitro and tumorigenesis in vivo. The gene set enrichment analysis was used to search the downstream pathway, luciferase reporter experiment was used to find the upstream regulatory factor of KIF26B.
In this study, we found that KIF26B was overexpressed both in HCC tissues and cell lines. High expression of KIF26B was associated with poor overall survival (OS), late TNM stage and poor differentiation. Loss of function experiments showed that suppression of KIF26B could inhibit cell viability, proliferation rate and invasion ability of HCC cells. KEGG and GO analysis showed that expression of KIF26B was highly relevant with PI3K/AKT signal pathway, and suppression of KIF26B could decrease the expression of m-TOR, p-PI3K and p-AKT. Further study demonstrated that expression of KIF26B was negative correlated with miR-450b-5p level in HCC tissues, and miR-450b-5p could inhibit cell viability, proliferation rate and invasion ability of HCC cells via targeted inhibiting KIF26B.
Our study demonstrated that miR-450-5p/KIF26B/AKT axis is critical for progression of HCC, and might provide novel prognostic biomarker and therapeutic target for HCC.
驱动蛋白家族成员26B（KIF26B）在多种实体瘤中发挥重要作用，然而，KIF26B在肝细胞癌（HCC）中的功能尚不清楚。
采用免疫化学、实时PCR和蛋白质印迹法检测HCC组织和细胞系中KIF26B的表达。运用SPSS19.0分析KIF26B表达与临床病理特征之间的相关性。通过CCK-8、Transwell、EDU、体外集落形成及体内肿瘤发生实验对KIF26B进行功能实验。利用基因集富集分析寻找下游通路，通过荧光素酶报告基因实验寻找KIF26B的上游调控因子。
在本研究中，我们发现KIF26B在HCC组织和细胞系中均过表达。KIF26B高表达与总生存期（OS）差、TNM分期晚及低分化相关。功能缺失实验表明，抑制KIF26B可抑制HCC细胞的活力、增殖率和侵袭能力。KEGG和GO分析显示，KIF26B的表达与PI3K/AKT信号通路高度相关，抑制KIF26B可降低m-TOR、p-PI3K和p-AKT的表达。进一步研究表明，HCC组织中KIF26B的表达与miR-450b-5p水平呈负相关，miR-450b-5p可通过靶向抑制KIF26B抑制HCC细胞的活力、增殖率和侵袭能力。
我们的研究表明，miR-450-5p/KIF26B/AKT轴对HCC的进展至关重要，可能为HCC提供新的预后生物标志物和治疗靶点。
