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Cited by 63Phagocytosis and Immune RegulationMicroRNA in disease regulationPancreatic and Hepatic Oncology Research

Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity

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Xi, Qing, Zhang, Jieyou, Yang, Guangze, Zhang, Lijuan, Chen, Ying, Wang, Chengzhi, Zhang, Zimu, Guo, Xiangdong +8 more·2020·Journal for ImmunoTherapy of Cancer
DOI 10.1136/jitc-2019-000253PMC PMC7279671
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Abstract

Background: Immune checkpoint blockade has emerged as a potential cancer immunotherapy. The “don’t eat me” signal CD47 in cancer cells binds signal regulatory protein-α on macrophages and prevents their phagocytosis. The role of miR-340 in pancreatic ductal adenocarcinoma (PDAC), especially in tumor immunity, has not been explored. Here, we examined the clinical and biological relevance of miR-340 and the molecular pathways regulated by miR-340 in PDAC. Methods: CD47 and miR-340 expression and the relationship with cancer patient survival were analyzed by bioinformatics. The mechanism of miR-340 action was explored through bioinformatics, luciferase reporter, qRT-PCR and western blot analyses. The effects of miR-340 on cancer cells were analyzed in terms of apoptosis, proliferation, migration and phagocytosis by macrophages. In vivo tumorigenesis was studied in orthotopic and subcutaneous models, and immune cells from the peripheral and tumor immune microenvironments were analyzed by flow cytometry. Depletion of macrophages was used to verify the role of macrophages in impacting the function of miR-340 in tumor progression. Results: miR-340 directly regulates and inversely correlates with CD47, and it predicts patient survival in PDAC. The restoration of miR-340 expression in pancreatic cancer cells was sufficient to downregulate CD47 and promote phagocytosis of macrophages, further inhibiting tumor growth. The overexpression of miR-340 promoted macrophages to become M1-like phenotype polarized in peripheral and tumor immune microenvironments and increased T cells, especially CD8 + T cells, contributing to the antitumor effect of miR-340. Conclusions: miR-340 is a key regulator of phagocytosis and antitumor immunity, and it could offer a new opportunity for immunotherapy for PDAC.

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  • Overexpression of miR-340 promoted macrophages to have the M1-like phenotype; miR-340 directly regulates and inversely correlates with CD47.

    “The overexpression of miR-340 promoted macrophages to have the M1-like phenotype. The authors noticed that miR-340 directly regulates and inversely correlates with CD47, the protein involved in cell migration, adhesion, and apoptosis [174].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [174]

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Cited by

Sorted by citations

Authors
Xi, Q., Zhang, J., Yang, G., Zhang, L., Chen, Y., Wang, C., Zhang, Z., Guo, X., Zhao, J., Xue, Z., Li, Y., Zhang, Q., Da, Y., Liu, L., Yao, Z., & Zhang, R.
Affiliations
  • Tianjin Medical University (CN)
  • Guangdong Pharmaceutical University (CN)
  • Tianjin Nankai Hospital (CN)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Zhang, Rongxin
ORCID
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2020-06
Volume
8
Issue
1
Pages
e000253
ISSN
2051-1426 (ISSN-L)
DOI
10.1136/jitc-2019-000253
PMC
PMC7279671
OpenAlex
W3033167704
Cited by
63
References
3
Citations by year
2026: 7 · 2025: 8 · 2024: 18 · 2023: 11 · 2022: 13 · 2021: 4 · 2020: 2
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81872320, 81272317, 31600730, 81602496,)
  • Guangdong Pharmaceutical University (2017KCXTD020)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
miR-340, CD47, pancreatic ductal adenocarcinoma, macrophage phagocytosis, tumor-associated macrophages, M1 macrophage polarization, antitumor immunity, CD8+ T cells, tumor immune microenvironment, microRNA regulation, patient survival
MeSH terms
Animals, Humans, Macrophages, Mice, Inbred C57BL, Pancreatic Neoplasms, Phagocytosis, Prognosis, Survival Rate, Apoptosis, Carcinoma, Pancreatic Ductal, Xenograft Model Antitumor Assays, MicroRNAs, Cell Proliferation, Mice, CD47 Antigen, Tumor Microenvironment

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