|Table of Contents|

lncRNA MEG3 regulates the NLRP3/caspase-1/GSDMD pathway to affect the sensitivity of triple-negative breast cancer to paclitaxel

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 04
Page:
597-602
Research Field:
Publishing date:

Info

Title:
lncRNA MEG3 regulates the NLRP3/caspase-1/GSDMD pathway to affect the sensitivity of triple-negative breast cancer to paclitaxel
Author(s):
YU Bing1 ; YANG Xu2 ; CHEN Zhimeng2 ; LEI Meng2
1.Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China;2.College of Science,Nanjing Forestry University,Jiangsu Nanjing 210037,China.
Keywords:
maternally expressed gene 3; NLR family; Pyrin domain containing protein 3/cysteinyl aspartate specific proteinase 1/gasdermin D; triple-negative breast cancer; paclitaxel; sensitivity
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2023.04.002
Abstract:
Objective:To explore the effect of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) on the sensitivity of triple-negative breast cancer (TNBC) to paclitaxel (PTX) by regulating the NLR family,Pyrin domain containing protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (caspase-1)/gasdermin D (GSDMD) pathway.Methods:TNBC drug-resistant cells MDA-MB-231/R were induced by gradually increasing the dose of PTX intermittent action method,and qRT-PCR was used to detect the expression of lncRNA MEG3.MDA-MB-231 cells were divided into control group (untransfected+PTX),Vector group (empty vector+PTX),pcDNA3.1-MEG3 group (pcDNA3.1-MEG3 expression vector+PTX),pcDNA3.1-MEG3+BAY11-7082 group (pcDNA3.1-MEG3 expression vector+PTX+5 μmol/L NLRP3 inhibitor BAY11-7082).qRT-PCR was used to detect the expression of lncRNA MEG3 after transfection.CCK-8 method was used to detect the proliferation of MDA-MB-231 cells.The pyroptosis of MDA-MB-231 cells was observed by immunofluorescence staining and scanning electron microscope (SEM).Western blot was used to detect the protein expression of NLRP3/caspase-1/GSDMD pathway in MDA-MB-231 cells.In vivo tumorigenic assay was used to detect tumor mass.Results:Compared with MDA-MB-231 cells,the expression level of lncRNA MEG3 in MDA-MB-231/R cells was significantly reduced (P＜0.05).Compared with the control group,the cell proliferation inhibition rate,number of GSDMD-N+cells,cell pyroptosis,cell apoptosis rate and the expression level of NLRP3,cleaved-caspase 1/caspase-1,GSDMD-N/GSDMD proteins in the pcDNA3.1-MEG3 group increased significantly,and IC50,tumor mass reduced significantly (P＜0.05).Compared with the pcDNA3.1-MEG3 group,the cell proliferation inhibition rate,number of GSDMD-N+cells,cell pyroptosis,cell apoptosis rate and the expression level of NLRP3,cleaved-caspase 1/caspase-1,GSDMD-N/GSDMD proteins in the pcDNA3.1-MEG3+BAY11-7082 group reduced significantly,and IC50,tumor mass increased significantly (P＜0.05).Conclusion:Up-regulating the expression of lncRNA MEG3 can promote the pyroptosis of MDA-MB-231 cells by activating the NLRP3/caspase-1/GSDMD pathway,thereby increasing the sensitivity of TNBC to PTX.

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Memo

Memo:
National Natural Science Foundation of China(No.21877061）；国家自然科学基金面上项目（编号：21877061）
Last Update: 1900-01-01