Layered double hydroxide-loaded si-NEAT1 regulates paclitaxel resistance and tumor-associated macrophage polarization in breast cancer by targeting miR-133b/PD-L1.
10.12122/j.issn.1673-4254.2025.08.16
- Author:
Zhaojun ZHANG
1
;
Qiong WU
1
;
Miaomiao XIE
1
;
Ruyin YE
1
;
Chenchen GENG
1
;
Jiwen SHI
1
;
Qingling YANG
1
;
Wenrui WANG
1
;
Yurong SHI
2
Author Information
1. Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu 233030, China.
2. Department of Biochemistry and Molecular Biology, Bengbu Medical University, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
M2 macrophage polarization;
PD-L1;
breast cancer;
layered double hydroxide;
lncRNA NEAT1;
miR-133b;
paclitaxel resistance
- MeSH:
Humans;
MicroRNAs/genetics*;
RNA, Long Noncoding/genetics*;
Paclitaxel/pharmacology*;
Breast Neoplasms/metabolism*;
Drug Resistance, Neoplasm;
B7-H1 Antigen/metabolism*;
Cell Line, Tumor;
Female;
Tumor-Associated Macrophages;
Apoptosis;
Cell Proliferation;
Macrophages;
Cell Movement
- From:
Journal of Southern Medical University
2025;45(8):1718-1731
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer.
METHODS:qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed.
RESULTS:SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages.
CONCLUSIONS:LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
