miR‐144‐3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1

Abstract

AbstractAerobic glycolysis is a unique mark of cancer cells, which enables therapeutic intervention in cancer. Forkhead box K1 (FOXK1) is a transcription factor that facilitates the progression of multiple cancers including hepatocellular carcinoma (HCC). Nevertheless, it is unclear whether or not FOXK1 can affect HCC cell glycolysis. This study attempted to study the effect of FOXK1 on HCC cell glycolysis. Expression of mature miRNAs and mRNAs, as well as clinical data, was downloaded from The Cancer Genome Atlas‐Liver hepatocellular carcinoma (TCGA‐LIHC) dataset. FOXK1 and miR‐144‐3p levels were assessed through quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot. Targeting of the relationship between miR‐144‐3p and FOXK1 was verified via a dual‐luciferase assay. Pathway enrichment analysis of FOXK1 was performed by Gene Set Enrichment Analysis (GSEA). Cell function assays revealed the glycolytic ability, cell viability, migration, invasion, cell cycle, and apoptosis of HCC cells in each treatment group. Bioinformatics analysis suggested that FOXK1 was upregulated in tissues of HCC patients, while the upstream miR‐144‐3p was downregulated in tumour tissues. Dual‐luciferase assay implied a targeting relationship between miR‐144‐3p and FOXK1. Cellular experiments implied that silencing FOXK1 repressed HCC cell glycolysis, which in turn inhibited the HCC malignant progression. Rescue assay confirmed that miR‐144‐3p repressed glycolysis in HCC cells by targeting FOXK1, and then repressed HCC malignant progression. miR‐144‐3p/FOXK1 axis repressed malignant progression of HCC via affecting the aerobic glycolytic process of HCC cells. miR‐144‐3p and FOXK1 have the potential to become new therapeutic targets for HCC, which provide new insights for HCC treatment.