ArticleCell cycle (Georgetown, Tex.)2015
miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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Who cites it
55 citing papers in PubMed, 82 citations in OpenAlex.
- Review
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Genetic association of miR-146a, miR-196a2, and miR-499 polymorphisms with hepatocellular carcinoma risk in an Eastern Chinese population.Frontiers in oncology · 2026Article
- Roles of exosome-mediated macrophage polarization in the hepatocellular carcinoma progression.Frontiers in immunology · 2026Review
- Mechanisms of Immune Checkpoint Inhibitor Resistance in Hepatocellular Carcinoma and Strategies for Reversal.Cancers · 2025Review
- Recent Advances in Cancer Immunotherapy Aided by Regulatory Non-Coding RNA: A Review.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Identification of pyroptosis-associated miRNAs in the immunoscape and prognosis of hepatocellular carcinoma.BMC cancer · 2024Article
- Tofacitinib Regulates Endostatin via Effects on CD147 and Cathepsin S.International journal of molecular sciences · 2024Article
- Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?Seminars in liver disease · 2024Review
- Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions.Frontiers in genetics · 2024Article
- The progress of research on immune checkpoint inhibitor resistance and reversal strategies for hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2023Review
- Review
- SHFM1 deficiency suppresses esophageal squamous cell carcinomas progression via modulating NF‑κB signaling and enhancing nature killer cell‑mediated tumor surveillance.Experimental and therapeutic medicine · 2023Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Immune cell-derived extracellular vesicular microRNAs induce pancreatic beta cell apoptosis.Heliyon · 2022Article
- Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients.International journal of molecular sciences · 2022Article
- Noncoding RNA-mediated molecular bases of chemotherapy resistance in hepatocellular carcinoma.Cancer cell international · 2022Review
- Noncoding RNA-mediated macrophage and cancer cell crosstalk in hepatocellular carcinoma.Molecular therapy oncolytics · 2022Review
- miR-146a Dysregulates Energy Metabolism During Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs (miRNAs) play an important role in tumorigenesis, but their role in tumor-induced immune suppression is largely unknown. STAT3 signaling, a key pathway mediating immune suppression in the tumor microenvironment, is responsible for the transcription of several important miRNAs. In this study, we observed that miR-146a, a known important regulator of immune responses, was downregulated by blocking activated STAT3 in hepatocellular carcinoma (HCC) cells. Furthermore, miR-146a inhibition in HCC cells not only altered the STAT3 activation-associated cytokine profile but also reversed HCC-induced NK cell dysfunction in vitro and improved the anti-tumor effect of lymphocytes in vivo. Importantly, ChIP and luciferase reporter assays confirmed that STAT3 directly bound to the miR-146a promoter and induced miR-146a expression. These findings indicated that miR-146a expression was regulated by aberrantly activated STAT3 in HCC cells and exerted negative effects on anti-tumor immune response, which resulted in the upregulation of cytokines such as TGF-β, IL-17, VEGF and downregulation of type I IFN to create an immunosuppressive microenvironment. This further insight into understanding the mechanism responsible for tumor-induced immune suppression highlights the potential application of miR-146a as a novel immunotherapeutic target for HCC.
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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.