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Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells
Gang Zhao1, Jiawei Chen, Yanqiu Deng
1Department of Pathology, The First People's Hospital, Shanghai Jiaotong University, Shanghai, China. zhaog69@sjtu.edu.cn
Abstract:
N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.
Insights
N-myc downstream regulated gene 1 (NDRG1) knockdown enhances cancer cell invasion and metastasis. NDRG1 regulates numerous genes indirectly, impacting complex tumor invasion processes.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- N-myc downstream regulated gene 1 (NDRG1) plays a critical role in regulating tumor invasion.
- Understanding NDRG1's regulatory mechanisms is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of NDRG1 in regulating tumor cell invasion and metastasis.
- To identify genes and pathways affected by NDRG1 knockdown in cancer cells.
Main Methods:
- shRNA technology was employed to suppress NDRG1 expression in cervical (CaSki) and ovarian (HO-8910PM) cancer cell lines.
- In vitro assays assessed cell adhesion, migration, and invasion.
- cDNA microarray analysis identified differentially expressed genes.
- Network analysis (BisoGenet) explored gene regulatory relationships.
Main Results:
- NDRG1 knockdown significantly enhanced tumor cell adhesion, migration, and invasion without affecting proliferation.
- Microarray analysis revealed 96 deregulated genes, including common upregulated genes (e.g., LPXN, DDR2, COL6A1, IL6, IL8) and one downregulated gene (CLCA2), associated with enhanced invasion.
- NDRG1 knockdown reduced the expression of pro-invasion genes like MMP7, TMPRSS4, and CTSK.
- Network analysis suggested NDRG1 regulates invasion effectors indirectly.
Conclusions:
- NDRG1 plays a complex role in regulating cancer cell invasion and metastasis.
- NDRG1 influences multiple genes and pathways involved in tumor progression.
- Targeting NDRG1 may offer therapeutic potential for managing cancer invasion and metastasis.
