Research on the Mechanism of the lncRNA DLX6-AS1/miR-26a/PTEN Axis in Regulating the Activation of Hepatic Stellate Cells in Post-hepatitis Liver Fibrosis: An Analysis Based on Systematic Validation and Clinical Translation Methods
Abstract
Objective: To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis. Methods: Systematic studies were conducted using cellular and animal models through causal validation, bivariate experiments, single-cell sequencing, ROC analysis of clinical samples, and humanized mouse models. Results: LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a, promoting hepatic stellate cell activation in a dose/time-dependent manner; the axis demonstrated excellent diagnostic performance (AUC > 0.9), and its inhibitors effectively reversed fibrosis in vivo. Conclusion: This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.
References
Ortiz C, Schierwagen R, Schaefer L, et al., 2021, Extracellular Matrix Remodeling in Chronic Liver Disease. Current Tissue Microenvironment Reports, 2(3): 41–52.
Bedossa P, Paradis V, 2003, Liver Extracellular Matrix in Health and Disease. Journal of Pathology, 200(4): 504–515.
Bataller R, Brenner D, 2005, Liver Fibrosis. Journal of Clinical Investigation, 115(2): 209–218.
Qian Y, Song W, Wu X, et al., 2021, DLX6 Antisense RNA 1 Modulates Glucose Metabolism and Cell Growth in Gastric Cancer by Targeting microRNA-4290. Digestive Diseases and Sciences, 66(2): 460–473.
Qu G, Li X, Jin R, et al., 2024, MicroRNA-26a Alleviates Tubulointerstitial Fibrosis in Diabetic Kidney Disease by Targeting PAR4. Journal of Cellular and Molecular Medicine, 28(3): e18099.
Bian E, Huang C, Ma T, et al., 2012, DNMT1-Mediated PTEN Hypermethylation Confers Hepatic Stellate Cell Activation and Liver Fibrogenesis in Rats. Toxicology and Applied Pharmacology, 264(1): 13–22.
Yang Y, Chen Y, Feng D, et al., 2024, Ficus hirta Vahl. Ameliorates Liver Fibrosis by Triggering Hepatic Stellate Cell Ferroptosis Through the GSH/GPX4 Pathway. Journal of Ethnopharmacology, 334: 118557.
Wang P, Li J, Ji M, et al., 2024, The Vitamin D Receptor Mitigates Carbon Tetrachloride-Induced Liver Fibrosis by Downregulating YAP. J Hazard Mater, 478: 135480.
Yao Y, Zuo X, Shao F, et al., 2024, Jaceosidin Inhibits the Progression of Hepatic Fibrosis by Suppressing the VGLL3/HMGB1/TLR4 Signaling Pathway. Phytomedicine, 128: 155502.
Qin H, Yang Y, Jiang B, et al., 2021, Cancer-Associated Fibroblasts Upregulate SOX9 in Prostate Cancer to Promote Tumor Progression Through the HGF/c-Met-FRA1 Signaling Pathway. FEBS J, 288(18): 5406–5429.
Liu X, Peng D, Cao Y, et al., 2021, The Upregulated lncRNA DLX6-AS1 Drives Hepatocellular Carcinoma Progression via the miR-513c/Cul4A/ANXA10 Axis. Cancer Gene Ther, 28(5): 486–501.
Zhao R, Yuan H, Jiang Y, et al., 2025, Development and Validation of an Integrative Risk Identification Model Based on 54 Biomarkers for Multi-Cancer in 42,666 Individuals: A Population-Based Prospective Study to Guide Advanced Screening Strategies. Biomark Res, 13(1): 101.
Hebert S, 1999, Molecular Mechanisms. Semin Nephrol, 19(6): 504–523.
