The micro RNA, miR-21, is overexpressed in many human cancers, and accumulating evidence indicates that miR-21 has oncogenic activity. Here we report that the cytokine IFNa/b rapidly induced the miR-21 transcript in several human and mouse cell lines. Pathways known to be involved in regulating cell death were identified as downstream targets for miR-21, including PTEN expression and Akt activation. Most interesting, we found that miR-21 plays a key role in suppressing IFN-induced apoptosis. Thus, manipulation of miR-21 may be an important novel way to modulate the sensitivity of various forms of cancer to chemotherapeurtic agents as well as cytokines, and provides a rationale for combining miR-21 knockdown with these agents. A miR21 knockdown lentivirus has been developed to study miR21 oncogenic activity.