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Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion
Jian-Jun Ma1, Ling-Min Kong, Cheng-Gong Liao
1Department of Urology Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, People's Republic of China. majj001@126.com
Abstract:
Members of the NDRG (N-Myc downstream-regulated) gene family have been shown to play a variety of roles in human malignancies. Recently, it was shown decreased expression in clear cell renal cell carcinoma (CCRCC) and inhibited cell proliferation, but the role of the NDRG2 in CCRCC invasion has not been described. We examined the expression of NDRG2 protein in CCRCC samples and the association between NDRG2 expression and CCRCC patients survival. Real-time RT-PCR and immunohistochemical analysis were used to measure NDRG2 expression in 60 paired CCRCC and adjacent normal tissues. Changes in cell invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. We found that NDRG2 expression is significantly down-regulated in CCRCC at mRNA and protein levels in a manner negatively associated with aggressive tumor behaviors, such as TNM stage (P = 0.003), Fuhrman's grade (P = 0.024), tumor invasion (P = 0.001) and tumor recurrence (P = 0.004), as well as shorter patient survival rates (P = 0.0041). Furthermore, NDRG2 could suppress CCRCC cell invasion through regulating MMP-9 expression and activity. So, these results suggest that NDRG2 can inhibit extracellular matrix-based tumor cell invasion and thereby play important roles in suppressing tumor metastasis in CCRCC. NDRG2 expression may also be a significant prognostic indicator for CCRCC.
Insights
N-Myc downstream-regulated gene 2 (NDRG2) is significantly downregulated in clear cell renal cell carcinoma (CCRCC), inhibiting tumor cell invasion and metastasis. Lower NDRG2 expression correlates with poorer patient survival, suggesting its prognostic value in CCRCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The N-Myc downstream-regulated gene (NDRG) family plays diverse roles in human cancers.
- NDRG2's function in clear cell renal cell carcinoma (CCRCC) invasion is largely uncharacterized.
- Previous studies noted NDRG2's decreased expression and inhibited proliferation in CCRCC.
Purpose of the Study:
- To investigate NDRG2 protein expression in CCRCC tissues.
- To determine the association between NDRG2 expression and patient survival in CCRCC.
- To elucidate NDRG2's role in CCRCC cell invasion and metastasis.
Main Methods:
- Real-time RT-PCR and immunohistochemistry to quantify NDRG2 mRNA and protein levels in 60 paired CCRCC and normal tissues.
- In vitro assays using adenovirus and siRNA to manipulate NDRG2 expression and assess effects on cell invasion.
- Analysis of MMP-9 expression and activity.
Main Results:
- NDRG2 expression was significantly downregulated at both mRNA and protein levels in CCRCC compared to normal tissues.
- Lower NDRG2 expression correlated negatively with advanced TNM stage, Fuhrman's grade, tumor invasion, and recurrence.
- NDRG2 suppressed CCRCC cell invasion by regulating MMP-9 expression and activity, and was associated with shorter patient survival.
Conclusions:
- NDRG2 inhibits extracellular matrix-based tumor cell invasion, playing a crucial role in suppressing metastasis in CCRCC.
- NDRG2 downregulation is linked to aggressive tumor behavior and poor prognosis in CCRCC patients.
- NDRG2 expression serves as a potential prognostic biomarker for CCRCC.
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