MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for cleavage or repression of translation. This study shows that miR-21 is highly overexpressed in human glioblastoma (GBM), a highly malignant brain tumor. miR-21 levels were significantly elevated in GBM tissues, early-passage cultures, and six established GBM cell lines compared to nonneoplastic brain tissues and cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured GBM cells triggered caspase activation and increased apoptotic cell death, suggesting that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes. The study also examined the expression of miR-21 in various brain tissues and cell lines, finding that it was strongly elevated in GBM samples compared to control tissues. miR-21 expression was also increased in several commonly used GBM cell lines. In contrast, lower levels of miR-21 were found in other primary brain tumors, suggesting that very high levels of this miRNA are more typical of GBM. To study the biological significance of miR-21 overexpression, the researchers used a loss-of-function approach in GBM cell lines. They employed two strategies to suppress miR-21: 2'-O-methyl-oligonucleotides and LNA/DNA-mixed antisense oligonucleotides. Both methods effectively reduced miR-21 expression and led to a significant decrease in cell number and increased apoptosis in GBM cells. These findings suggest that miR-21 functions as an antiapoptotic factor in GBM cells, potentially by blocking the expression of genes involved in apoptosis. The study also highlights the potential of miRNAs as important factors in the development or maintenance of the neoplastic state. The results indicate that miR-21 may act as a micro-oncogene in GBM by blocking expression of key apoptosis-enabling genes. This study is the first to ascribe a function to an aberrantly expressed miRNA in human neoplasia. The findings suggest that miRNAs are critical to the biology and possibly to the treatment of human malignancies.MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for cleavage or repression of translation. This study shows that miR-21 is highly overexpressed in human glioblastoma (GBM), a highly malignant brain tumor. miR-21 levels were significantly elevated in GBM tissues, early-passage cultures, and six established GBM cell lines compared to nonneoplastic brain tissues and cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured GBM cells triggered caspase activation and increased apoptotic cell death, suggesting that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes. The study also examined the expression of miR-21 in various brain tissues and cell lines, finding that it was strongly elevated in GBM samples compared to control tissues. miR-21 expression was also increased in several commonly used GBM cell lines. In contrast, lower levels of miR-21 were found in other primary brain tumors, suggesting that very high levels of this miRNA are more typical of GBM. To study the biological significance of miR-21 overexpression, the researchers used a loss-of-function approach in GBM cell lines. They employed two strategies to suppress miR-21: 2'-O-methyl-oligonucleotides and LNA/DNA-mixed antisense oligonucleotides. Both methods effectively reduced miR-21 expression and led to a significant decrease in cell number and increased apoptosis in GBM cells. These findings suggest that miR-21 functions as an antiapoptotic factor in GBM cells, potentially by blocking the expression of genes involved in apoptosis. The study also highlights the potential of miRNAs as important factors in the development or maintenance of the neoplastic state. The results indicate that miR-21 may act as a micro-oncogene in GBM by blocking expression of key apoptosis-enabling genes. This study is the first to ascribe a function to an aberrantly expressed miRNA in human neoplasia. The findings suggest that miRNAs are critical to the biology and possibly to the treatment of human malignancies.