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MicroRNAs in tumor development and cancer therapy

Our group has studied posttranscriptional gene regulation in cancer for many years. Originally, we focused on studying recurring genetic abnormalities in hematological malignancies. Working on a critical region lost in over 50% of all cases of chronic lymphocytic leukemia (CLL), we identified the ncRNA gene DLEU2 in 1997 (Liu et al., 1997). This ncRNA was found to function as a critical host gene for the miRNAs first described to be tumor-suppressive, miR-15a and miR-16-1 (Lerner et al., 2009). Interestingly, the DLEU2 gene is also an antisense gene for RFP2/TRIM13, an E3 ubiquitin ligase essential for endoplasmic reticulum-associated degradation (ERAD) (Corcoran et al., 2004; Lerner et al., 2007). The past couple of years, we have studied the role of miRNAs in tumor development, identifying novel critical miRNA regulators for several tumor-suppressor genes and oncogenes, including cyclin D1, cyclin E, hCdc4/Fbw7 and Noxa (Lerner et al., 2012; Lerner et al., 2009; Lerner et al., 2011). Furthermore, the group has characterized global miRNA expression profiles in several malignancies and also assessed the impact of common treatment regimens on miRNA expression in acute lymphoblastic leukemia (Harada et al., 2012). At present, we are analyzing the functional interplay between miRNAs and long non-coding RNAs.