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?p?Selleckchem Autophagy inhibitor microRNA-34 (miR-34) is highly evolutionarily conserved (Corney et?al., 2007?and?He et?al., 2007). In mammals, the miR-34 family is composed of three processed microRNAs (miRNAs) that are encoded by two different genes: miR-34a is encoded by its own transcript, whereas PRDX5 miR-34b and miR-34c share a common primary transcript as a cluster. Due to the high homology among these three members, they have many similar targets and may be functionally redundant (He et?al., 2007). miR-34 was the first miRNA reported to be directly transactivated by tumor suppressor p53 (aka Trp53/TP53) and is considered to be an important component of the p53 network (Hermeking, 2012). In addition to a transactivation-dependent decrease in expression levels in p53-deficient tumors, mir-34 is also deleted or epigenetically downregulated in multiple cancer cell lines and human malignancies ( Bader, 2012?and?Hermeking, 2012). Ectopic expression of miR-34 has been shown to counteract various oncogenic processes by regulating target genes that function in cell cycle, Selleck Tariquidar apoptosis, senescence, cell migration, and invasion ( Hermeking, 2012). Furthermore, treatment with miR-34 mimics inhibits cancer formation in transplantation experiments ( Bader, 2012?and?Liu et?al., 2011). Contrary to the expectations raised from experiments based on nonphysiological approaches, such as exogenous miR-34 introduction and miR-34 knockdown, only minor defects have been reported in studies of mice with targeted inactivating mutations of mir-34 ( Concepcion et?al., 2012?and?Wei et?al., 2012). Moreover, complete genetic inactivation of miR-34 did not impair the p53 response in a variety of ex?vivo and in?vivo assays ( Concepcion et?al., 2012). Most surprisingly, no increase in spontaneous or irradiation-induced carcinogenesis has been observed in mice lacking all mir-34 genes by 18?month of age ( Concepcion et?al., 2012). The absence of all mir-34 genes also did not accelerate B cell lymphomagenesis in mice overexpressing c-Myc under the control of the E�� promoter ( Concepcion et?al.