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Updated: Jun 22, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
ISG15 promotes tumor progression via IL6/JAK2/STAT3 signaling pathway in ccRCC
Wei Xie1, Yuanfeng Zhang1, Zhechuan Zhang1
1Department of Urology, The Second Affiliated Hospital of Chongqing Medical University, Linjiang Road. 74, Jiangbei, Chongqing, China.
Abstract:
Although renal cell carcinoma (RCC) is a prevalent type of cancer, the most common pathological subtype, clear cell renal cell carcinoma (ccRCC), still has poorly understood molecular mechanisms of progression. Moreover, interferon-stimulated gene 15 (ISG15) is associated with various types of cancer; however, its biological role in ccRCC remains unclear.This study aimed to explore the role of ISG15 in ccRCC progression.ISG15 expression was upregulated in ccRCC and associated with poor prognosis. RNA sequence analysis and subsequent experiments indicated that ISG15 modulated IL6/JAK2/STAT3 signaling to promote ccRCC proliferation, migration, and invasion. Additionally, our animal experiments confirmed that sustained ISG15 knockdown reduced tumor growth rate in nude mice and promoted cell apoptosis. ISG15 modulates the IL6/JAK2/STAT3 pathway, making it a potential therapeutic target and prognostic biomarker for ccRCC.
Insights
Interferon-stimulated gene 15 (ISG15) promotes clear cell renal cell carcinoma (ccRCC) progression by activating the IL6/JAK2/STAT3 pathway. ISG15 upregulation correlates with poor prognosis, suggesting its potential as a therapeutic target and biomarker in ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC), presents poorly understood progression mechanisms.
- Interferon-stimulated gene 15 (ISG15) is implicated in various cancers, but its specific role in ccRCC is unclear.
Purpose of the Study:
- To investigate the role and mechanism of ISG15 in ccRCC progression.
- To evaluate ISG15 as a potential prognostic biomarker and therapeutic target for ccRCC.
Main Methods:
- Analysis of ISG15 expression in ccRCC tissues.
- RNA sequencing and experimental validation of ISG15's downstream signaling pathways.
- In vivo studies using nude mice to assess the impact of ISG15 knockdown on tumor growth and apoptosis.
Main Results:
- ISG15 expression was significantly upregulated in ccRCC tissues and correlated with poor patient prognosis.
- ISG15 was found to modulate the IL6/JAK2/STAT3 signaling pathway, promoting ccRCC cell proliferation, migration, and invasion.
- ISG15 knockdown in vivo reduced tumor growth rate and increased apoptosis in ccRCC xenografts.
Conclusions:
- ISG15 plays a crucial role in promoting ccRCC progression through the IL6/JAK2/STAT3 pathway.
- ISG15 represents a promising therapeutic target and a valuable prognostic biomarker for clear cell renal cell carcinoma.
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