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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Ming Li1, Ying Wang1, Yongsheng Song1

  • 11 Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, China ; 2 Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA ; 3 Department of Nuclear Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.

Chinese Journal of Cancer Research = Chung-Kuo Yen Cheng Yen Chiu
|September 19, 2014
PubMed
Abstract

Insights

DNA methyltransferase 1 (DNMT1) is overexpressed in clear cell renal cell carcinoma (ccRCC) and linked to poor prognosis. Inhibiting DNMT1 shows promise for ccRCC treatment by reducing cancer cell proliferation and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer.
  • Dysregulation of DNA methyltransferase 1 (DNMT1) is implicated in various cancers.
  • Understanding DNMT1's role in ccRCC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the contribution of DNA methyltransferase 1 (DNMT1) expression to clear cell renal cell carcinoma (ccRCC) progression.
  • To evaluate the impact of DNMT1 on ccRCC cell biology and its potential as a therapeutic target.

Main Methods:

  • Immunohistochemistry was used to compare DNMT1 expression in 89 ccRCC and 22 normal tissue samples.
  • ccRCC cell lines (786-0 and Caki-1) were treated with DNMT1 siRNA to assess effects on cell viability, apoptosis, colony formation, and invasion.
  • Statistical analysis was performed to correlate DNMT1 expression with clinical parameters.

Main Results:

  • DNMT1 protein expression was significantly higher in ccRCC tissues compared to normal tissues (56.2% vs. 27.3%, P=0.018).
  • DNMT1 expression correlated strongly with tumor size, stage, grade, lymph node metastasis, vascular invasion, recurrence, and patient prognosis.
  • Knockdown of DNMT1 inhibited ccRCC cell viability, induced apoptosis, and reduced colony formation and invasion.

Conclusions:

  • Elevated DNMT1 protein expression in ccRCC is associated with aggressive disease and poor patient outcomes.
  • DNMT1 plays a critical role in the proliferation and invasion of renal cancer cells.
  • Targeting DNMT1 represents a potential therapeutic strategy for ccRCC, demonstrating efficacy in vitro by reducing cell viability and invasion while increasing apoptosis.
Keywords:
Clear cell renal cell carcinoma (ccRCC)DNA methyltransferase 1 (DNMT1)immunohistochemistrysiRNA

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