RETRACTED: miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα
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Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3'UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα.
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Overexpression of miR-181a promotes M2 polarization by targeting KLF6 and C/EBPα.
“Bi et al. showed that overexpression of miR-181a promotes M2 polarization by targeting KLF6 and C/EBPα [164].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [164]
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Yamamoto, Y., Sugimura, R., Watanabe, T., Shigemori, S., Okajima, T., Nigar, S., Namai, F., Sato, T., Ogita, T., & Shimosato, T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01049 · Cited by 15 · see citing works
MiR-451a enhances the phagocytosis and affects both M1 and M2 polarization in macrophages
Liu, X., Zhang, D., Wang, H., Ren, Q., Li, B., Wang, L., & Zheng, G. (2021) · Cellular Immunology · doi:10.1016/j.cellimm.2021.104377 · Cited by 12 · see citing works
Peng, Y., Li, X., Liu, H., Deng, X., She, C., Liu, C., Wang, X., & Liu, A. (2020) · Nanoscale Research Letters · doi:10.1186/s11671-020-03416-8 · Cited by 11 · see citing works
Self-citationRetractedChen, S., Ma, B., Li, X., Zhang, K., Wei, Y., Du, B., Liu, X., Wei, R., Li, X., & Nian, H. (2022) · iScience · doi:10.1016/j.isci.2022.105176 · Cited by 11 · see citing works
LINC00703 Acts as a Tumor Suppressor via Regulating miR-181a/KLF6 Axis in Gastric Cancer
Yang, H., Peng, M., Li, Y., Zhu, R., Li, X., & Qian, Z. (2019) · Journal of the Korean Gastric Cancer Association · doi:10.5230/jgc.2019.19.e43 · Cited by 9 · see citing works
Chen, Y., Huang, Y., Chen, C., Wen, Y., Tsai, R., & Chen, C. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.1.17 · Cited by 9 · see citing works
Cismaru, C. A., Pîrlog, R., Călin, G. A., & Berindan‐Neagoe, I. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10428-7 · Cited by 8 · see citing works
Macrophage Switching in Pregnancy: Regulatory Mechanisms Governing Term Labour and Preterm Birth
Prakash, G. R., Vaidhya, A., Deepthi, V., Rathore, L. S., Panigrahi, M., Madhu, C. L., Singh, T. U., & Parida, S. (2025) · American Journal of Reproductive Immunology · doi:10.1111/aji.70123 · Cited by 8 · see citing works
Signal Mechanisms of M2 Macrophage Activation
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miRNAs: the genetic regulators of immunity
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Adenovirus 14p1 induced changes in miRNA expression increases lung immunopathogenesisPreprint
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An Overview of MicroRNA Mediated Regulation of TAM and EMT Pathway in Progression of Breast Cancer
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Chen, I.-H., Feng, J.-Y., Shu, C., Chang, C.-J., Tseng, Y.-H., Wang, P.-H., & Pan, S. (2026) · Pulmonology · doi:10.1080/25310429.2026.2704386
- Authors
- Bi, J., Zeng, X., Zhao, L., Wei, Q., Yu, L., Wang, X., Yu, Z., Cao, Y., Shan, F., & Wei, M.
- Affiliations
- China Medical University (CN)
- Corresponding author
- Wei, Minjie
- Venue
- Molecular Therapy - Nucleic Acids
- Publisher
- Elsevier BV
- Published
- 2016
- Volume
- 5
- Issue
- 9
- Pages
- e368
- ISSN
- 2162-2531 (ISSN-L)
- PMC
- PMC5056994
- OpenAlex
- W2526085451
- Cited by
- 63
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 12 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 10
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs (RCS 14-232)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- miR-181a, macrophage polarization, M2 macrophages, M1 macrophages, KLF6, C/EBPα, metastasis, tumor cell migration and invasion, microRNA target regulation, 3' untranslated region, retraction
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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