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Updated: Jul 17, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Integrative analysis of deoxyribonuclease 1-like 3 as a potential biomarker in renal cell carcinoma
Minghuan Ge1, Hengcheng Zhu1, Huajie Song1
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
Background:
Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), is insensitive to radiotherapy and chemotherapy after surgery. Deoxyribonuclease 1-like 3 (DNASE1L3), an endonuclease that cleaves both membrane-encapsulated single- and double-stranded DNA, suppresses cell cycle progression, proliferation and metabolism in hepatocellular carcinoma cells. There is currently no established link between DNASE1L3 and RCC inhibition. We are gonging to explored the mechanism underlying the relationship between DNASEL1L3 and RCC.
Methods:
RNA sequencing data for RCC tissue and peritumoral tissue were downloaded from The Cancer Genome Atlas database and analyzed. The expression levels of DNASE1L3 in RCC and normal samples were verified using the Gene Expression Omnibus (GEO) database, Human Protein Atlas database and western blotting. The role and potential mechanism of DNASE1L3 were investigated by analysis of immune-related databases and wound healing, invasion, cell counting kit 8 and immunofluorescence assays.
Results:
We revealed that DNASE1L3 expression was downregulated in RCC group compared with control group [The Cancer Genome Atlas (TCGA): 7.98 vs. 10.87, P<0.001]. Meanwhile, DNASE1L3 expression correlated with the clinical characteristics of patients. Patients with low DNASE1L3 expression had worse survival (P<0.001) and larger (r=-0.32, P<0.001) and heavier tumors (r=-0.17, P<0.001). DNASE1L3 overexpression inhibited the proliferation (786-O: 0.135±0.014 vs. 0.322±0.027, P<0.001) and invasion (786-O: 1,479±134 vs. 832±67, P<0.05) of RCC cells. The expression of DNASE1L3 was significantly correlated with the tumor immune microenvironment and drug sensitivity in ccRCC. Moreover, the level of the key phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway protein P-AKT was decreased in the group of cells transfected with DNASE1L3.
Conclusions:
This study strongly suggest that DNASE1L3 may be a promising potential biomarker for the diagnosis and treatment of ccRCC patients.
Insights
Deoxyribonuclease 1-like 3 (DNASE1L3) is downregulated in clear cell renal cell carcinoma (ccRCC), correlating with worse survival. Overexpression of DNASE1L3 inhibits ccRCC proliferation and invasion, suggesting its potential as a diagnostic and therapeutic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype and is largely unresponsive to conventional treatments.
- Deoxyribonuclease 1-like 3 (DNASE1L3) is an endonuclease known to suppress cell growth in other cancers, but its role in ccRCC was previously unestablished.
Purpose of the Study:
- To investigate the role and underlying mechanism of DNASE1L3 in clear cell renal cell carcinoma (ccRCC).
- To explore DNASE1L3 as a potential biomarker for ccRCC diagnosis and treatment.
Main Methods:
- RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed for DNASE1L3 expression in ccRCC.
- Functional assays including wound healing, invasion, cell counting kit 8, and immunofluorescence were performed.
- Correlation analysis with clinical characteristics, tumor immune microenvironment, and drug sensitivity was conducted.
Main Results:
- DNASE1L3 expression was significantly downregulated in ccRCC tissues compared to normal tissues.
- Lower DNASE1L3 expression correlated with poorer patient survival, larger tumor size, and heavier tumor weight.
- Overexpression of DNASE1L3 suppressed ccRCC cell proliferation and invasion, and affected the PI3K/AKT signaling pathway.
Conclusions:
- DNASE1L3 plays a suppressive role in ccRCC progression.
- DNASE1L3 demonstrates potential as a promising biomarker for ccRCC diagnosis and treatment strategies.
