Yang YF, Liu QX, Su WH, Zang B, Liu BQ, Zhao CY, Han YB, Liu LW, Leung PSC, Liu B. Plasma exosomal miR-137 activates natural killer cells in primary biliary cholangitis by targeting NFATC1. World J Hepatol 2026; 18(6): 116738 [DOI: 10.4254/wjh.116738]
Corresponding Author of This Article
Bin Liu, Professor, Department of Rheumatology, Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China. binliu72314@163.com
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Immunology
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research-article
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Yang YF, Liu QX, Su WH, Zang B, Liu BQ, Zhao CY, Han YB, Liu LW, Leung PSC, Liu B. Plasma exosomal miR-137 activates natural killer cells in primary biliary cholangitis by targeting NFATC1. World J Hepatol 2026; 18(6): 116738 [DOI: 10.4254/wjh.116738]
World J Hepatol. Jun 27, 2026; 18(6): 116738 Published online Jun 27, 2026. doi: 10.4254/wjh.116738
Plasma exosomal miR-137 activates natural killer cells in primary biliary cholangitis by targeting NFATC1
Yi-Fei Yang, Qi-Xuan Liu, Wen-Hao Su, Bo Zang, Bing-Qian Liu, Chen-Yang Zhao, Yi-Bing Han, Ling-Wei Liu, Patrick S C Leung, Bin Liu
Yi-Fei Yang, Bo Zang, Bing-Qian Liu, Chen-Yang Zhao, Yi-Bing Han, Ling-Wei Liu, Bin Liu, Department of Rheumatology, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Qi-Xuan Liu, Graduate Group of Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, United States
Wen-Hao Su, Department of Thoracic Surgery, Qingdao West Coast New Area Central Hospital, Qingdao 266555, Shandong Province, China
Patrick S C Leung, Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, CA 95616, United States
Author contributions: Yang YF and Liu B edited the first draft of the manuscript; Liu QX, Su WH, and Zang B performed the material preparation, data collection, and analyses; Liu BQ, Zhao CY, Han YB, and Liu LW accessed the methodology; All authors commented on previous versions of the manuscript, contributed to the study conception and design, and read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81671600 and No. 81241094; the Natural Science Foundation of Shandong Province, No. ZR2023MH066.
Institutional review board statement: This study was approved by the Ethics Committee of Affiliated Hospital of Qingdao University (No. QYFYWZLL29594).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. The original data presented in the study are included in the article/Supplementary Figure 1.
Corresponding author: Bin Liu, Professor, Department of Rheumatology, Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China. binliu72314@163.com
Received: November 19, 2025 Revised: February 25, 2026 Accepted: April 28, 2026 Published online: June 27, 2026 Processing time: 212 Days and 7.4 Hours
Abstract
BACKGROUND
Primary biliary cholangitis (PBC) is an autoimmune liver disease involving dysregulated natural killer (NK) cell activity.
AIM
To investigate whether microRNAs (miRNA) modulate NK cell activation and granzyme B secretion in PBC via the nuclear factor of activated T cell (NFATC) pathway, focusing on the regulatory role of miR-137-3p.
METHODS
Peripheral blood samples from 168 patients with PBC and 74 healthy controls were analyzed. NK cells were isolated, and miRNA expression was quantified via quantitative polymerase chain reaction. Flow cytometry assessed cluster of differentiation (CD) molecule expression, whereas dual luciferase assays validated miR-137-3p binding to the NFATC1 gene.
RESULTS
There were significantly lower Ct values (indicating higher expression) for miR-137-3p, miR-124-3p, and miR-506-3p in NK cells from patients with PBC vs cells from healthy controls (all P < 0.05). The miR-137-3p directly bound NFATC1, enhancing granzyme B secretion (348.59 ± 7.47 pg/mL vs 373.92 ± 15.50 pg/mL; P < 0.05) and increasing the number of CD16+ NK cells (73.2% vs 46.8; P < 0.05) compared to controls.
CONCLUSION
Exosomal miR-137-3p promotes NK cell activation in PBC by targeting NFATC1, driving CD16 expression and granzyme B secretion. These miRNAs, particularly miR-137-3p, may serve as novel diagnostic biomarkers or therapeutic targets for PBC.
Core Tip: This study identifies elevated exosomal microRNA-137-3p (miR-137-3p) in primary biliary cholangitis (PBC) plasma as a key driver of natural killer cell hyperactivation. Mechanistically, miR-137-3p directly targets and inhibits nuclear factor of activated T cell 1, leading to upregulation of the activation marker cluster of differentiation 16 and enhanced secretion of the cytotoxic molecule granzyme B. These findings define miR-137-3p as a novel diagnostic biomarker and suggest that targeting the miR-137-3p/nuclear factor of activated T cell 1 axis could be a promising therapeutic strategy for PBC by alleviating natural killer cell-mediated bile duct injury.
