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Updated: Dec 17, 2025

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Downregulation of RUNX3 has a poor prognosis and promotes tumor progress in kidney cancer
Jianbo Zheng1, Yanhui Mei2, Guangsheng Zhai3
1Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of Urology, Central Hospital of Zibo, Zibo, Shandong, China.
Background:
Kidney cancer usually shows no symptoms until the tumor is relatively large, and current drugs fail to stop the tumor recurrence. The transcriptional factor Runt-related transcription factor 3 (RUNX3) has been reported to function as a tumor suppressor in many types of cancers.
Methods:
Kidney cancer and adjacent normal tissues were collected from 12 patients to test the expression of RUNX3 by real-time quantitative PCR, immunoblotting, and immunohistochemistry. Promoter methylation status of RUNX3 was determined using methylation analysis from 103 patient samples. Kidney cancer cell lines and xenograft mouse model were used to investigate the promoter methylation and cancer progression through inhibitor treatment and loss/gain-of-function experiments.
Results:
RUNX3 was significantly downregulated in kidney cancer tissues and cells, which could be elevated by higher methylation status at its promoter region. RUNX3 promoter methylation was positively correlated with poor prognosis of kidney cancer. RUNX3 loss-of-function promoted the cell proliferation, migration, and invasion of kidney cancer cells, in contrast, RUNX3 overexpression inhibited the cancer cell progression. This study provides the first instance of the effect of RUNX3 expression and its promoter methylation status on kidney cancer.
Conclusion:
Targeting RUNX3 pathway and its promoter methylation are potential therapeutic strategies to treat kidney cancer.
Insights
Runt-related transcription factor 3 (RUNX3) is downregulated in kidney cancer due to promoter methylation, promoting tumor progression. Restoring RUNX3 may offer new therapeutic strategies for kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Kidney cancer often lacks early symptoms and is prone to recurrence.
- The tumor suppressor role of Runt-related transcription factor 3 (RUNX3) is established in various cancers.
Purpose of the Study:
- To investigate the role of RUNX3 expression and its promoter methylation in kidney cancer.
- To explore the potential of RUNX3 as a therapeutic target for kidney cancer.
Main Methods:
- Quantitative PCR, immunoblotting, and immunohistochemistry were used to assess RUNX3 expression in patient tissues and cell lines.
- Methylation analysis of the RUNX3 promoter was performed on 103 patient samples.
- In vitro and in vivo experiments (cell lines, xenograft models) examined the impact of RUNX3 modulation on cancer progression.
Main Results:
- RUNX3 expression was significantly downregulated in kidney cancer tissues and cells.
- Increased RUNX3 promoter methylation correlated with decreased RUNX3 expression and poorer kidney cancer prognosis.
- RUNX3 loss-of-function enhanced, while overexpression inhibited, kidney cancer cell proliferation, migration, and invasion.
Conclusions:
- RUNX3 acts as a tumor suppressor in kidney cancer, with its activity suppressed by promoter methylation.
- Targeting the RUNX3 pathway and its promoter methylation presents a promising therapeutic strategy for kidney cancer treatment.
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