驱动蛋白家族成员C3（KIFC3）通过上皮-间质转化（EMT）和AKT/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路调控肝细胞癌进展。

KIFC3 regulates progression of hepatocellular carcinoma via EMT and the AKT/mTOR pathway.

作者信息

Lu Shimin, Liu Yinghui, Tian Shan, He Yang, Dong Weiguo

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China.

Department of Infectious Disease, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Exp Cell Res. 2023 May 1;426(1):113564. doi: 10.1016/j.yexcr.2023.113564. Epub 2023 Mar 21.

DOI:10.1016/j.yexcr.2023.113564

PMID:36948354

Abstract

INTRODUCTION

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. Despite an overall downward trend in cancer mortality, HCC-related mortality continues to increase. KIFC3 is involved in cell division and cancers. However, the role of KIFC3 in HCC has yet to be elucidated.

METHODS

A total of 36 cases of HCC tissues, 4 HCC cell lines, and TCGA databases were searched to explore the expression of KIFC3 in HCC. Subsequently, Western blot analysis, immunofluorescence, bioinformatic analysis, molecular docking, and Co-IP were performed to investigate the molecular mechanisms of KIFC3 in HCC.

RESULT

We found that the expression of KIFC3 was upregulated in HCC, and high KIFC3 expression was related to poor overall survival. In addition, the knockdown of KIFC3 inhibited the proliferation, migration, and invasion of HCC cells in vitro, and impeded the growth of HCC in vivo, while overexpression of KIFC3 in HCC cells revealed the opposite effect. Mechanistically, KIFC3 promotes the progression of HCC through the PI3K/AKT/mTOR signalling. And KIFC3 had slight effect on the protein expression of p-PI3K, p-AKT and p-mTOR in TRIP13-ablated or LY294002-treated HCC cells. The KIFC3 knockdown could further enhance the inhibitory effect of LY294002.

CONCLUSION

Our data revealed that KIFC3 is upregulated in HCC and may serve as a novel biomarker for predicting survival in HCC patients. Targeting KIFC3 may serve as a novel therapeutic strategy for HCC patients.

摘要

引言

肝细胞癌（HCC）是全球癌症相关死亡的第四大主要原因。尽管癌症死亡率总体呈下降趋势，但HCC相关死亡率仍在持续上升。KIFC3参与细胞分裂和癌症。然而，KIFC3在HCC中的作用尚未阐明。

方法

共检索36例HCC组织、4种HCC细胞系和TCGA数据库，以探究KIFC3在HCC中的表达。随后，进行蛋白质印迹分析、免疫荧光、生物信息学分析、分子对接和免疫共沉淀，以研究KIFC3在HCC中的分子机制。

结果

我们发现KIFC3在HCC中表达上调，且KIFC3高表达与总体生存率低相关。此外，敲低KIFC3可抑制HCC细胞在体外的增殖、迁移和侵袭，并在体内阻碍HCC的生长，而在HCC细胞中过表达KIFC3则显示出相反的效果。机制上，KIFC3通过PI3K/AKT/mTOR信号通路促进HCC的进展。并且KIFC3对TRIP13缺失或LY294002处理的HCC细胞中p-PI3K、p-AKT和p-mTOR的蛋白表达影响轻微。敲低KIFC3可进一步增强LY294002的抑制作用。