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.

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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