Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase-2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA-HK2 or pCDNA3.1-HK2, followed by GA treatment. A Cell Counting Kit-8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription-quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2-knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated-AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.
To investigate the effect of long noncoding RNA (LINC01419)/miR‐485‐5p/LSM4 on the malignant behavior of hepatocellular carcinoma (HCC) cells. The expressions of LINC01419, miR‐485‐5p, and LSM4 were determined in HCC at the cellular and clinical levels, and cell biological behavior was evaluated. The relationships between LINC01419, miR‐485‐5p, and LSM4 were predicted and verified. Additionally, the subcellular localization of LINC01419 in HCC cells was analyzed. Finally, an animal experiment was conducted to confirm the effect of LINC01419 silencing on tumor growth. in HCC tissues and cells, LINC01419 and LSM4 were increasingly expressed, but miR‐485‐5p was decreasingly expressed. LINC01419 negatively regulated miR‐485‐5p‐ and miR‐485‐5p‐targeted LSM4. LINC01419 was localized in the cytoplasm of HCC cells. Downregulation of miR‐485‐5p or upregulation of LSM4 reversed the inhibition of HCC cell malignant behavior by LINC01419 interference. LINC01419 sponges miR‐485‐5p to upregulate LSM4 expression, thereby facilitating the biological behavior of HCC cells.
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