MicroRNA-21 targets tumor suppressor genes in invasion and metastasis MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding mRNAs post-transcriptionally. Previous studies showed that miR-21 functions as an oncogene, promoting tumorigenesis by regulating the tumor suppressor gene tropomyosin 1 (TPM1). This study investigated the role of miR-21 in cell invasion and metastasis. Suppression of miR-21 in metastatic breast cancer MDA-MB-231 cells reduced invasion and lung metastasis. Ectopic expression of TPM1 also reduced cell invasion. Two additional direct targets of miR-21, programmed cell death 4 (PDCD4) and maspin, were identified. Both PDCD4 and maspin reduced invasiveness of MDA-MB-231 cells. Expression of PDCD4 and maspin inversely correlated with miR-21 in human breast tumors, suggesting miR-21 regulates these genes. These results indicate that miR-21 promotes tumor invasion and metastasis by targeting multiple tumor suppressor genes. Suppression of miR-21 may provide a novel approach for treating advanced cancers. Keywords: cell invasion, miRNA, mir-21, post-transcriptional regulation, MDA-MB-231, tumorigenesis, metastasis, gene silencing, PDCD4, maspin Cell Research (2008) 18:350-359. doi: 10.1038/cr.2008.24; published online 12 February 2008 MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding mRNAs by repressing translation or causing mRNA degradation. Mature miRNAs are about 22 nucleotides long and target multiple genes. miRNAs regulate diverse cellular processes, including differentiation, proliferation, and apoptosis. Deregulation of miRNAs affects normal cell growth and development, leading to disorders including human malignancies. miRNAs can function as tumor suppressors or oncogenes depending on their targets. Tumor suppressive miRNAs are usually underexpressed in tumors, while oncogenic miRNAs are overexpressed. miR-21 is an oncogenic miRNA overexpressed in tumors. Previous studies showed that miR-21 promotes breast cancer cell growth by suppressing PTEN and TPM1. These genes are also involved in cell migration and invasion, suggesting miR-21 may affect invasion and metastasis. This study provides evidence that miR-21 regulates invasion and metastasis by targeting metastasis-related tumor suppressor genes such as TPM1, PDCDMicroRNA-21 targets tumor suppressor genes in invasion and metastasis MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding mRNAs post-transcriptionally. Previous studies showed that miR-21 functions as an oncogene, promoting tumorigenesis by regulating the tumor suppressor gene tropomyosin 1 (TPM1). This study investigated the role of miR-21 in cell invasion and metastasis. Suppression of miR-21 in metastatic breast cancer MDA-MB-231 cells reduced invasion and lung metastasis. Ectopic expression of TPM1 also reduced cell invasion. Two additional direct targets of miR-21, programmed cell death 4 (PDCD4) and maspin, were identified. Both PDCD4 and maspin reduced invasiveness of MDA-MB-231 cells. Expression of PDCD4 and maspin inversely correlated with miR-21 in human breast tumors, suggesting miR-21 regulates these genes. These results indicate that miR-21 promotes tumor invasion and metastasis by targeting multiple tumor suppressor genes. Suppression of miR-21 may provide a novel approach for treating advanced cancers. Keywords: cell invasion, miRNA, mir-21, post-transcriptional regulation, MDA-MB-231, tumorigenesis, metastasis, gene silencing, PDCD4, maspin Cell Research (2008) 18:350-359. doi: 10.1038/cr.2008.24; published online 12 February 2008 MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding mRNAs by repressing translation or causing mRNA degradation. Mature miRNAs are about 22 nucleotides long and target multiple genes. miRNAs regulate diverse cellular processes, including differentiation, proliferation, and apoptosis. Deregulation of miRNAs affects normal cell growth and development, leading to disorders including human malignancies. miRNAs can function as tumor suppressors or oncogenes depending on their targets. Tumor suppressive miRNAs are usually underexpressed in tumors, while oncogenic miRNAs are overexpressed. miR-21 is an oncogenic miRNA overexpressed in tumors. Previous studies showed that miR-21 promotes breast cancer cell growth by suppressing PTEN and TPM1. These genes are also involved in cell migration and invasion, suggesting miR-21 may affect invasion and metastasis. This study provides evidence that miR-21 regulates invasion and metastasis by targeting metastasis-related tumor suppressor genes such as TPM1, PDCD