Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Unlabelled: MicroRNA-221 (miR-221) is one of the most frequently and consistently up-regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR-221 may act as a tumor promoter. To demonstrate this, we developed a transgenic (TG) mouse model that exhibits an inappropriate overexpression of miR-221 in the liver. Immunoblotting and immunostaining confirmed a concomitant down-regulation of miR-221 target proteins. This TG model is characterized by the emergence of spontaneous nodular liver lesions in approximately 50% of male mice and by a strong acceleration of tumor development in 100% of mice treated with diethylnitrosamine. Similarly to human hepatocellular carcinoma, tumors are characterized by a further increase in miR-221 expression and a concomitant inhibition of its target protein-coding genes (i.e., cyclin-dependent kinase inhibitor [Cdkn]1b/p27, Cdkn1c/p57, and B-cell lymphoma 2-modifying factor). To validate the tumor-promoting effect of miR-221, we showed that in vivo delivery of anti-miR-221 oligonucleotides leads to a significant reduction of the number and size of tumor nodules.
Conclusions: This study not only establishes that miR-221 can promote liver tumorigenicity, but it also establishes a valuable animal model to perform preclinical investigations for the use of anti-miRNA approaches aimed at liver cancer therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/hep.25747 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dynamic regulation of IL-33 in the obesity pathogenesis: Spatiotemporal specificity and functional paradoxes.
Diabetes Res Clin Pract
September 2025
Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011 Hunan, China. Electronic address:
Obesity is a complex chronic metabolic disease closely associated with inflammatory responses and insulin resistance. As a member of the IL-1 cytokine family, Interleukin-33(IL-33) binds to its receptor suppression of tumorigenicity 2 (ST2) and plays a crucial role in regulating the adipose tissue immune microenvironment and maintaining metabolic homeostasis. However, its role in obesity exhibits spatiotemporal specificity and functional paradoxes.
View Article and Find Full Text PDFThe Dichotomous Role of Tertiary Lymphoid Structures in Hepatocellular Carcinoma: From Spatial Location to Clinical Implications.
Immunol Invest
August 2025
Department of Liver Surgery, Affiliated Cancer Hospital of Fudan University, Shanghai, China.
Background: Tertiary lymphoid structures (TLSs) function as ectopic immune centers in non-lymphoid tissues and are a key area of research in tumor immunology, particularly in hepatocellular carcinoma (HCC). However, the role of TLSs in HCC shows significant heterogeneity; intratumoral TLSs (iTLSs) are linked to favorable outcomes and immune therapy responses, while peritumoral TLSs may be dysfunctional or promote tumor progression. This spatial paradox is a core scientific question for understanding and leveraging TLSs in HCC treatment.
View Article and Find Full Text PDFHypoxia suppressed the Siglec-5 signaling in TAMs via modulating the balance of SHP2/SYK activation in hepatocellular carcinoma.
Sci Rep
August 2025
The People's Hospital of Xishuangbanna Dai Autonomous Prefecture Medical Laboratory, 4 Gai Lan Nan Road, Jinghong Street, Jinghong City, Xishuangbanna Dai Autonomous Prefecture, 666100, Yunnan Province, China.
Objective: To investigate the effects of Siglec-5 on hepatocellular carcinoma and the mechanism of action. The interactions and expression changes between Siglec-5 and Siglec-14 not only affect immune cell function, but may also influence tumor progression. A deeper understanding of the mechanisms regulating their balance could provide new insights and strategies for hepatocellular carcinoma treatment.
View Article and Find Full Text PDFLiver-Specific Extracellular Matrix Enables High-Fidelity Patient-Derived Hepatocellular Carcinoma Xenograft Models.
Biomater Res
August 2025
Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
Patient-derived tumor xenograft (PDX) models serve as powerful tools in oncology research owing to their ability to capture patient-specific tumor heterogeneity and clinical behavior. However, the conventional matrices derived from murine tumors, commonly used to generate PDX models, suffer from key limitations such as lack of tissue specificity, high production costs, and inconsistent batch quality. In response, our study investigates the use of decellularized liver extracellular matrix (Liver ECM) as a biomimetic alternative that more accurately recapitulates the native hepatic microenvironment.
View Article and Find Full Text PDFSACF and GILA assays on AML12 cells show limited predictive value for mouse liver genotoxicity.
Toxicol Appl Pharmacol
August 2025
Novartis Biomedical Research, Basel, Switzerland. Electronic address:
Hepatocellular carcinoma (HCC) has been observed in neonatal mice following the integration of recombinant Adeno-Associated Viruses (rAAV) into the Rian locus. rAAV-related oncogenic risk for patients remains unclear, and the lack of relevant in vitro methods hinders its proper assessment. The soft agar colony-forming (SACF) assay and the growth in low attachment assay (GILA) monitor anchorage-independent growth, a hallmark of transformed adherent cells, and have been previously proposed to assess the tumorigenicity of CRISPR/Cas9-edited human MCF10A cells.
View Article and Find Full Text PDF