MicroRNA-138-5p Suppresses Non-small Cell Lung Cancer Cells by Targeting PD-L1/PD-1 to Regulate Tumor Microenvironment
Open accessAbstract
Non-small cell lung cancer (NSCLC) is still challenging for treatment owing to immune tolerance and evasion. MicroRNA-138 (miR-138) not only acts as a tumor suppressor to inhibit tumor cell proliferation and migration but also regulates immune response. The regulatory mechanism of miR-138 in NSCLC remains not very clear. Herein, we demonstrated that miR-138-5p treatment decreased the growth of tumor cells and increased the number of tumor-infiltrated DCs. miR-138-5p not only down-regulated the expression of cyclin D3 (CCND3), CCD20, Ki67, and MCM in A549/3LL cells, but also regulated the maturation of DCs in A549-bearing nude mice and the 3LL-bearing C57BL/6 mouse model, and DCs' capability to enhance T cells to kill tumor cells. Furthermore, miR-138-5p was found to target PD-L1 to down-regulate PD-L1 on tumor cells to reduce the expression of Ki67 and MCM in tumor cells and decrease the tolerance effect on DCs. miR-138-5p also directly down-regulates the expression of PD-L1 and PD-1 on DCs and T cells. Similar results were obtained from isolated human non-small cell lung cancer (NSCLC) cells and DCs. Thus, miR-138-5p inhibits tumor growth and activates the immune system by down-regulating PD-1/PD-L1 and it is a promising therapeutic target for NSCLC.
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Various critical transcription factors, including HIF-1α, c-MYC, NF-kB, STAT3, c-JUN, and miR-138-5p, have been shown to transcriptionally regulate PD-L1 expression.
“Various critical transcription factors, including HIF-1α, c-MYC, NF-kB, STAT3, c-JUN, and miR-138-5p have been shown to transcriptionally regulate PD-L1 expression25–30.”
From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [30]
The Results section reports that miR-138-5p targets and down-regulates PD-L1, supporting its inclusion as a regulator. But the same section reports no significant change in PD-L1 gene expression despite lower protein expression, while the Introduction describes microRNAs as acting through mRNA degradation or translation inhibition. The paper therefore does not support calling miR-138-5p a transcription factor or saying it transcriptionally regulates PD-L1; it does not establish the other listed factors. (LLM, conf=0.88)
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References 68 · Cited by 55
- Authors
- Song, N., Li, P., Song, P., Li, Y., Zhou, S., Su, Q., Li, X., Yu, Y., Li, P., Feng, M., Zhang, M., & Lin, W.
- Affiliations
- Shandong Provincial Hospital (CN)
- Xizang Minzu University (CN)
- Shandong Tumor Hospital (CN)
- Jinan University (CN)
- Corresponding author
- Lin, Wei
- ORCID
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-07-10
- Volume
- 8
- Pages
- 540-540
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7365935
- OpenAlex
- W3036777065
- Cited by
- 55
- References
- 68
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 4 · 2022: 17 · 2021: 16 · 2020: 1
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Update notices
- corrigendum (2020-08-21)
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- non-small cell lung cancer, PD-L1, PD-1, tumor microenvironment, dendritic cell maturation, tumor-infiltrating dendritic cells, tumor immune tolerance, tumor cell proliferation, Ki-67, MCM, cyclin D3, cancer immunotherapy
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