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LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation

Lining Zhou1,2, Yu Tian1,2, Fang Guo3

  • 1International Genome Center, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.

Cancer Immunology, Immunotherapy : CII
|February 17, 2020
PubMed

Insights

LincRNA-p21 promotes breast cancer progression by reprogramming tumor-associated macrophages (TAMs). Inhibiting lincRNA-p21 in TAMs may offer a new therapeutic strategy for breast cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor-associated macrophages (TAMs) play a critical role in breast cancer progression and metastasis.
  • Understanding the mechanisms that regulate TAM functional phenotypes within the tumor microenvironment is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the role of lincRNA-p21 in regulating TAM function in breast cancer.
  • To elucidate the molecular mechanisms by which lincRNA-p21 influences TAM polarization and breast cancer progression.

Main Methods:

  • LncRNA microarray analysis to identify lncRNA profiles in TAMs.
  • Flow cytometry to assess TAM surface markers.
  • Fluorescence in situ hybridization (FISH) and immunofluorescence to determine co-localization of lincRNA-p21, p53, and MDM2.
  • In vivo studies using PyVT-MMTV and BALB/c mouse models.

Main Results:

  • LincRNA-p21 was significantly upregulated in macrophages educated by 4T1 breast cancer cells.
  • Knockdown of lincRNA-p21 promoted macrophage polarization towards a pro-inflammatory M1 phenotype.
  • LincRNA-p21 knockdown in TAMs led to increased cancer cell apoptosis and reduced tumor cell migration and invasion.
  • Adoptive transfer of lincRNA-p21 knockdown macrophages alleviated breast cancer progression in vivo.

Conclusions:

  • LincRNA-p21 is a key regulator of TAM function in the breast tumor microenvironment.
  • LincRNA-p21 influences TAM polarization via the MDM2-p53 pathway, affecting NF-κB and STAT3 signaling.
  • Targeting lincRNA-p21 in TAMs presents a potential novel therapeutic strategy for breast cancer.
Keywords:
Breast cancerTAMsTumor microenvironmentlincRNA-p21p53

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