ArticleFrontiers in cell and developmental biology2020
PD-L1 Is a Tumor Suppressor in Aggressive Endometrial Cancer Cells and Its Expression Is Regulated by miR-216a and lncRNA MEG3.
Article in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis.Frontiers in oncology · 2021Pooled it
- sMICA/sMICB and Immune Checkpoint in Endometriosis: Toward a Minimally Invasive Diagnostic Model Based on Machine Learning.Biomedicines · 2026Article
- LncRNAs signatures in gynecological cancers: ovarian and endometrial cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Assessment of the PD-1/PD-L1/PD-L2 Immune Checkpoints Pathway in Endometrial Cancer and Its Clinical Significance.Cancers · 2025Article
- Intrinsic PDL1 Signaling Modulates TGFBI-Mediated Growth Suppression in Lung Adenocarcinoma.Cancer science · 2025Article
- Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Building a Hand-Curated ceRNET for Endometrial Cancer, Striving for Clinical as Well as Medicolegal Soundness: A Systematic Review.Non-coding RNA · 2025Review
- Engineered PD-L1 co-expression in PD-1 knockout and MAGE-C2-targeting TCR-T cells augments the cytotoxic efficacy toward target cancer cells.Scientific reports · 2025Article
- PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Adaptive Significance of Non-coding RNAs: Insights from Cancer Biology.Molecular biology and evolution · 2025Review
- Deciphering the mysteries of MEG3 LncRNA and its implications in genitourinary cancers.Frontiers in oncology · 2025Review
- Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.Molecular and cellular biochemistry · 2024Review
- The Promotive and Inhibitory Role of Long Non-Coding RNAs in Endometrial Cancer Course-A Review.Cancers · 2024Review
- MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways.Cancer cell international · 2024Review
- Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance.International journal of molecular sciences · 2023Review
- PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023Review
- PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers.BMC cancer · 2023Article
- Loss of MEG3 contributes to the enhanced migration and invasion in arsenic-induced carcinogenesis through NQO1/FSCN1 pathway.American journal of cancer research · 2023Article
- Overexpression of lncRNA-MEG3 inhibits endometrial cell proliferation and invasion via miR-21-5p/DNMT3B/Twist.Clinics (Sao Paulo, Brazil) · 2023Article
- The Biological Roles and Molecular Mechanisms of Long Non-Coding RNA MEG3 in the Hallmarks of Cancer.Cancers · 2022Review
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPoorly differentiated endometrioid adenocarcinoma and serous adenocarcinoma represent an aggressive subtype of endometrial cancer (EC). Programmed death-ligand-1 (PD-L1) was known to exhibit a tumor cell-intrinsic function in mediating immune-independent tumor progression. However, the functional relevance of tumor cell-intrinsic PD-L1 expression in aggressive EC cells and the mechanisms regulating its expression remain unknown.
methodsPD-L1 expression in 65 EC tissues and 18 normal endometrium samples was analyzed using immunohistochemical staining. The effects of PD-L1 on aggressive EC cell growth, migration and invasion were investigated by cell functional assays. Luciferase reporter assays were used to reveal the microRNA-216a (miR-216a)-dependent mechanism modulating the expression of PD-L1.
resultsPositive PD-L1 expression was identified in 84% of benign cases but only in 12% of the EC samples, and the staining levels of PD-L1 in EC tissues were significantly lower than those in the normal tissues. Higher PD-L1 expression predicts favorable survival in EC. Ectopic expression of PD-L1 in aggressive EC cells results in decreased cell proliferation and the loss of mesenchymal phenotypes. Mechanistically, PD-L1 exerts the anti-tumor effects by downregulating MCL-1 expression. We found that PD-L1 levels in aggressive EC cells are regulated by miR-216a, which directly targets
conclusionThese results reveal an unappreciated tumor cell-intrinsic role for PD-L1 as a tumor suppressor in aggressive EC cells, and identify MEG3 and miR-216a as upstream regulators of PD-L1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.