Effect of miR-5589-5p on Apoptosis and Autophagy of Hepatocellular Carcinoma Cells by Targeting FOXK1

doi:10.19586/j.2095-2341.2025.0056

Current Biotechnology ›› 2025, Vol. 15 ›› Issue (6): 1086-1093.DOI: 10.19586/j.2095-2341.2025.0056

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Effect of miR-5589-5p on Apoptosis and Autophagy of Hepatocellular Carcinoma Cells by Targeting FOXK1

Ce JIANG¹, Yi LIU², Yalei ZHAO³, Xiangrong CHANG⁴()

^1.Department of Medical Laboratory，Shaanxi Provincial Rehabilitation Hospital，Xi′an 710065，China
^2.Department of Traditional Chinese Medicine，the First Affiliated Hospital of Xi'an Jiaotong University，Xi′an 710065，China
^3.Department of Infectious Diseases，the First Affiliated Hospital of Xi′an Jiaotong University，Xi′an 710065，China
^4.Department of Gastroenterology，Shaanxi Provincial Rehabilitation Hospital，Xi′an 710065，China

Received:2025-04-29 Accepted:2025-09-15 Online:2025-11-25 Published:2026-01-04
Contact: Xiangrong CHANG

Abstract

Abstract:

This study aimed to investigate the role and mechanism of miR-5589-5p on apoptosis and autophagy in hepatocellular carcinoma （HCC） cells. Bioinformatics analysis was employed to explore the differential expression of miR-5589-5p and FOXK1 in human HCC and their association with the prognosis of patients with HCC. miR-5589-5p mimics were used to upregulate miR-5589-5p levels. The levels of miR-5589-5p， protein expression levels of LC3， p62， Beclin-1， FOXK1， Bax， and Bcl-2 were detected. Cell apoptosis and autophagy were detected. Dual-luciferase reporter gene assay and RNA immunoprecipitation （RIP） were utilized to verify the binding of miR-5589-5p to the 3'-UTR of FOXK1. The results showed that miR-5589-5p was lowly expressed in human HCC （P0.05）， and a lower expression level of miR-5589-5p correlated with a poorer prognosis in HCC （P0.05）. In contrast， FOXK1 was highly expressed in HCC （P0.05）， and a higher expression level of FOXK1 was associated with a worse prognosis （P0.05）. Overexpression of miR-5589-5p significantly promoted cell apoptosis and autophagy. miR-5589-5p was confirmed to target the 3'-UTR of FOXK1. Overexpression of FOXK1 significantly inhibited the aforementioned effects of miR-5589-5p mimics （P0.05）. In conclusion， miR-5589-5p is lowly expressed in HCC and promotes apoptosis and autophagy in HCC cells by regulating FOXK1. This study lays an experimental foundation for further exploring the feasibility of miR-5589-5p as a predictive marker or therapeutic target for HCC.

Key words: miR-5589-5p, hepatocellular carcinoma, FOXK1, autophagy, apoptosis

摘要：

研究旨在探究miR-5589-5p对肝癌细胞凋亡和自噬的作用及机制。采用生物信息学分析miR-5589-5p、FOXK1在人肝细胞癌中的表达差异及其与肝癌患者预后的关系。采用miR-5589-5p mimics转染上调miR-5589-5p，检测miR-5589-5p及LC3、p62、Beclin-1、FOXK1、Bax、Bcl-2蛋白表达水平，检测细胞凋亡及自噬，双荧光素酶报告基因及RNA免疫共沉淀法检测miR-5589-5p与FOXK1 3′-UTR的结合。结果显示，miR-5589-5p在人肝细胞癌中低表达（P0.05），miR-5589-5p表达水平越低肝癌预后越差（P0.05）。FOXK1在人肝细胞癌中高表达（P0.05），FOXK1表达水平越高肝癌预后越差（P0.05）。miR-5589-5p过表达显著促进细胞凋亡和自噬（P0.05）。miR-5589-5p能靶向结合FOXK1的3'-UTR。在miR-5589-5p mimics转染的基础上过表达FOXK1，可显著抑制miR-5589-5p mimics的上述作用（P0.05）。综上，miR-5589-5p在肝癌中低表达，miR-5589-5p通过靶向FOXK1促进肝癌细胞凋亡和自噬。研究结果为进一步探讨miR-5589-5p作为肝细胞癌预测标志或治疗靶点提供了实验基础。

关键词: miR-5589-5p, 肝细胞癌, FOXK1, 自噬, 凋亡

CLC Number:

Q279

Ce JIANG, Yi LIU, Yalei ZHAO, Xiangrong CHANG. Effect of miR-5589-5p on Apoptosis and Autophagy of Hepatocellular Carcinoma Cells by Targeting FOXK1[J]. Current Biotechnology, 2025, 15(6): 1086-1093.

江策, 刘昳, 赵亚磊, 常香荣. miR-5589-5p靶向调控FOXK1对肝癌细胞凋亡和自噬的影响[J]. 生物技术进展, 2025, 15(6): 1086-1093.

Figures/Tables 6

Fig. 1 Expression level of miR-5589-5p in hepatocellular carcinoma and its relationship with prognosis

Fig. 2 Effect of miR-5589-5p overexpression on apoptosis of hepatocellular carcinoma cells

Fig. 3 Effect of miR-5589-5p overexpression on autophagy of hepatocellular carcinoma cells

Fig. 4 miR-5589-5p targets and regulates FOXK1

Fig. 5 Western blot detection of FOXK1 protein expression levels

Fig. 6 Effect of FOXK1 overexpression on apoptosis and autophagy in hepatocellular carcinoma cells

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Effect of miR-5589-5p on Apoptosis and Autophagy of Hepatocellular Carcinoma Cells by Targeting FOXK1

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