Detailed Abstract
[Liver Oral Presentation 3]
[LV OP 3-1] miR-4790-3p promotes the survival of hepatocellular carcinoma cells by inhibiting ZNF225 mRNA by enhancing autophagy
Ho Joong CHOI1, Tae Ho HONG1, Jung Hyun PARK2, Kee-Hwan KIM5, Dong Do YOU3, Jae Hyun HAN3, Kwang Yeol PAIK4, Say-June KIM*1
1Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Korea
2Department of Surgery, Eunpeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Korea
3Department of Surgery, St. Paul's Hospital, College of Medicine, the Catholic University of Korea, Korea
4Department of Surgery, Yeouido ST. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea
5Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Korea
Introduction : It is a challenge to overcome the low response rate of everolimus in the treatment of patients with hepatocellular carcinoma (HCC). To overcome this challenge, researchers combined everolimus with Ku0063794, the inhibitor of mTORC1 and mTORC2, to achieve higher anticancer effects.
Methods : However, the precise mechanism for the synergistic effects is not clearly determined yet. We first selected miRNAs that showed the most significant variation in expression according to the mono- and combination therapy of everolimus and Ku0063794. Subsequently, we determined the role of specific miRNAs in the anticancer effects of combination therapy against HepG2 cells through overexpressing or inhibiting the specific miRNAs.
Results : Compared to individual monotherapies, everolimus and Ku0063794 combination therapy significantly reduced viability, increased apoptosis, and reduced autophagy in HepG2 cells. The analysis of the miRNA array revealed that the expression of miR-4790-3p was significantly increased following everolimus monotherapy, decreased following Ku0063794 monotherapy, and significantly decreased following combination therapy. ZNF225, a target mRNA of miR-4790-3p, was significantly highly expressed in HepG2 cells following combination therapy.
Conclusions : miR-4790-3p promotes autophagy in HepG2 cells by inhibiting the expression of ZNF225. Everolimus and Ku0063794 combination therapy has superior anticancer effects against HCC cells, in part because it significantly reduces the expression of miR-4790-3p that plays an essential role in increasing autophagy.
Methods : However, the precise mechanism for the synergistic effects is not clearly determined yet. We first selected miRNAs that showed the most significant variation in expression according to the mono- and combination therapy of everolimus and Ku0063794. Subsequently, we determined the role of specific miRNAs in the anticancer effects of combination therapy against HepG2 cells through overexpressing or inhibiting the specific miRNAs.
Results : Compared to individual monotherapies, everolimus and Ku0063794 combination therapy significantly reduced viability, increased apoptosis, and reduced autophagy in HepG2 cells. The analysis of the miRNA array revealed that the expression of miR-4790-3p was significantly increased following everolimus monotherapy, decreased following Ku0063794 monotherapy, and significantly decreased following combination therapy. ZNF225, a target mRNA of miR-4790-3p, was significantly highly expressed in HepG2 cells following combination therapy.
Conclusions : miR-4790-3p promotes autophagy in HepG2 cells by inhibiting the expression of ZNF225. Everolimus and Ku0063794 combination therapy has superior anticancer effects against HCC cells, in part because it significantly reduces the expression of miR-4790-3p that plays an essential role in increasing autophagy.
SESSION
Liver Oral Presentation 3
Room A 7/28/2020 8:10 AM - 8:17 AM