BACKGROUND Breast cancer is a prevalent malignant tumor among women.Despite significant advancements in the development and implementation of various anti-breast cancer therapies,enhancing the efficacy of these drugs ...BACKGROUND Breast cancer is a prevalent malignant tumor among women.Despite significant advancements in the development and implementation of various anti-breast cancer therapies,enhancing the efficacy of these drugs while minimizing their toxicity remains a challenge.AIM To explore the functional impact of the targeted long chain non-coding RNA(LncRNA)of Chidamide on the activity of natural killer(NK)cells via programmed death-ligand 1(PD-L1),particularly focusing on the mechanisms by which NK cells influence breast cancer cells.METHODS This study screened the positive LncRNA molecule Linc01010 through highthroughput sequencing,which can counteract the pharmacological effects of Chidamide.Luciferase localization analysis revealed that the Linc01010 fragment was situated in the proximal exon 4-3 region,identified as its functionally active region.Electrophoretic mobility shift assays and RNA-protein pull-down experiments demonstrated the interaction between Chidamide-induced Linc01010 expression and the target protein mitogen-activated protein kinase kinase 6(MKK6).Western blotting and quantitative polymerase chain reaction analyses indicated that Chidamide enhanced the expression of the downstream effector PD-L1 by activating the corresponding p38-mitogen-activated protein kinases pathway.RESULTS While investigating the effects of the Chidamide-Linc01010-MKK6-PD-L1 axis on the immune cell line NK-92,we observed that tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)secretion was significantly inhibited by this response axis.Furthermore,reducing TRAIL secretion within the tumor microenvironment diminished the death effects in breast cancer cells induced by Chidamide.CONCLUSION Our study provides a robust foundation for improving the effectiveness of current anti-breast cancer medications and for identifying new targets related to drug resistance.展开更多
基金Supported by Natural Science Combination Foundation for Improving Innovation of Liaoning Province,No.2022-NLTS-14-01.
文摘BACKGROUND Breast cancer is a prevalent malignant tumor among women.Despite significant advancements in the development and implementation of various anti-breast cancer therapies,enhancing the efficacy of these drugs while minimizing their toxicity remains a challenge.AIM To explore the functional impact of the targeted long chain non-coding RNA(LncRNA)of Chidamide on the activity of natural killer(NK)cells via programmed death-ligand 1(PD-L1),particularly focusing on the mechanisms by which NK cells influence breast cancer cells.METHODS This study screened the positive LncRNA molecule Linc01010 through highthroughput sequencing,which can counteract the pharmacological effects of Chidamide.Luciferase localization analysis revealed that the Linc01010 fragment was situated in the proximal exon 4-3 region,identified as its functionally active region.Electrophoretic mobility shift assays and RNA-protein pull-down experiments demonstrated the interaction between Chidamide-induced Linc01010 expression and the target protein mitogen-activated protein kinase kinase 6(MKK6).Western blotting and quantitative polymerase chain reaction analyses indicated that Chidamide enhanced the expression of the downstream effector PD-L1 by activating the corresponding p38-mitogen-activated protein kinases pathway.RESULTS While investigating the effects of the Chidamide-Linc01010-MKK6-PD-L1 axis on the immune cell line NK-92,we observed that tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)secretion was significantly inhibited by this response axis.Furthermore,reducing TRAIL secretion within the tumor microenvironment diminished the death effects in breast cancer cells induced by Chidamide.CONCLUSION Our study provides a robust foundation for improving the effectiveness of current anti-breast cancer medications and for identifying new targets related to drug resistance.
