[Dihydromyricetin reverses Herceptin resistance by up-regulating miR-98-5p and inhibiting IGF1R/HER2 dimer formation in SKBR3 cells].

Abstract

OBJECTIVE:

To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells.

METHODS:

The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation.

RESULTS:

The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05).

CONCLUSION:

Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.

• Authors: M Zhang, C Guo, Y Chu, R Xu, F Yin, J Qian
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 42 Issue 2 Pg. 207-214 (Feb 20 2022) ISSN: 1673-4254 [Print] China
• PMID: 35365444 (Publication Type: Journal Article)

Chemical References

• Flavonols
• IGF1R protein, human
• MIRN98 microRNA, human
• MicroRNAs
• Receptor, IGF Type 1
• dihydromyricetin
• Trastuzumab

Topics

• Animals
• Cell Line, Tumor
• Flavonols (pharmacology)
• Humans
• Mice
• MicroRNAs (genetics, metabolism)
• Receptor, IGF Type 1
• Trastuzumab