shRNA acceleration of MYC-induced HCC corresponds with distinct changes in miRNA profiles. Microarray analysis was performed to detect changes in miRNA expression due to shRNA and/or MYC in livers of transgenic mice. Note the multiple changes in mice treated with high titer of the anti-p53 shRNA vector, that are not represented in animals treated with a nontoxic shRNA. Several of these miRNAs (especially upregulators) demonstrated comparable altered expression in livers treated with the toxic sAg-25 shRNA, that induced similar phenotypes and also accelerated tumorigenesis (see text and Supplementary Table S1). Also note the many differences between the MYC ON and OFF groups for a given shRNA, as well as the specific and MYC-independent response (decrease) of miR-805 to p53 RNAi (see text for details). HCC, hepatocellular carcinoma; miRNA, microRNA; RNAi, RNA interference; sAg, surface antigen; shRNA, short hairpin RNA.