miR-590-5p promotes liver cancer growth and chemotherapy resistance through directly targeting FOXO1

American Journal of Translational Research

Youyin Tang¹  Guiqing Jia² 

[1] Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital, Chengdu 610072, China;Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China

关键词: Liver cancer;    miR-590-5p;    FOXO1;    apoptosis;    cell cycle;    chemotherapy resistance;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

miR-590-5p functions as an onco-miR or an anti-onco-miR in various types of cancers. However, the exact role of miR-590-5p in liver cancer remains to be elucidated. In the present study, we explored the predictive role of miR-590-5p expression in liver cancer patients. In addition, CCK-8 assay, colony formation assay, and analysis of xenograft tumors were performed to investigate the biological effects of miR-590-5p in liver cancer. A direct target of miR-590-5p was identified based on a luciferase assay and further molecular experiments. Our results demonstrated that miR-590-5p was upregulated in malignant tissues of liver cancer patients and in liver cancer cell lines. miR-590-5p expression was found to be inversely correlated with disease-free survival of liver cancer patients. Furthermore, both in vitro and in vivo experiments showed that miR-590-5p knockdown inhibited the growth of HepG2 and Bel-7404 tumor cells by promoting apoptosis and cell cycle arrest. We also demonstrated that increasing of miR-590-5p in 5-Fu resistant patients and liver cancer cells, and knockdown of miR-590-5p enhances chemosensitivity to 5-Fu in liver cancer. FOXO1 was identified as a direct and necessary target of miR-590-5p during regulating liver cancer growth. Taken together, our findings provide insights into the role of miR-590-5p in liver cancer. Moreover, it is suggested that miR-590-5p can serve as a novel therapeutic target and predictive biomarker for liver cancer.

【 授权许可】

CC BY-NC