125I suppressed the Warburg effect viaregulating miR-338/PFKL axis in hepatocellular carcinoma - 01/10/19
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Iconographies | 7 |
Vidéos | 0 |
Autres | 0 |
Highlights |
• | 125I irradiation was decreased the Warburg effect in hepatocellular carcinoma. |
• | 125I irradiation inhibited malignant biological behavior of hepatocellular carcinoma cells. |
• | 125I irradiation increased the expression of miR-338 both in vitro and in vivo. |
• | Upregulation of miR-338 by 125I exerted antitumor effect by downregulating PFKL-mediated Warburg effect. |
Abstract |
Objectives |
Iodine-125 (125I) irradiation has been widely applied in the treatment of advanced multiple malignant tumors. However, the underlying mechanism of 125I exerted an anti-tumor effect on hepatocellular carcinoma (HCC) was largely unknown.
Methods |
In both HCCLM3 and SMMC-7721 cells, the effect of 125I irradiation on the glycolysis was detected. The mRNA in HCC tissues and cell lines were detected by RT-qPCR. Cell proliferation, invasion and migration, and apoptosis were examined by CCK-8, Transwell, wound healing assay and flow cytometry assay, respectively. The interaction between miR-338 and PFKL (6-phosphofructokinase) were verified by dual-luciferase reporter gene assay. Western blotting was used to detect the expression of glycolysis-related proteins. We also evaluated the effect of 125I seed implantation on the tumor growth and Warburg effect in vivo.
Results |
125I irradiation significantly decreased the Warburg effect, cell proliferation, invasion and migration, and induced apoptosis of HCCLM3 and SMMC-7721 cells. miR-338 was upregulated in HCC cells treated with 125I irradiation, which was a negative correlation with tumor size, tumor metastasis, and tumor development. Moreover, miR-338 directly interacted with PFKL and suppressed its expression. Mechanistically, 125I irradiation significantly decreased the Warburg effect and exhibited anti-tumorigenesis function through upregulating the inhibitory effect of miR-338 on PFKL expression.
Conclusion |
125I irradiation upregulated the suppression of miR-338 on PFKL to downregulate the Warburg effect and anti-tumorigenesis in HCC and provided a new potential strategy for HCC clinical treatment.
Le texte complet de cet article est disponible en PDF.Abbreviations : CCK-8, D90, DCR, ECAR, GLUT1, HCC, HK2, 125I, IC50, OCR, PFA, PFKL, PVDF
Keywords : Hepatocellular carcinoma, Warburg effect, 125I, miR-338/PFKL axis
Plan
Vol 119
Article 109402- novembre 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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