which the DLEU2 transcript and the miR-15a/16-1 cluster were separately re-expressed in the human I83E95 cell line that was derived from a 13q14−/− CLL. The results showed that miR-15a/16-1 expressing cells, but not those expressing DLEU2, were impaired in proliferation. In accord with this observation, miR-15a/16-1 expressing cells had a higher fraction of cells in the G0/G1 phase compared with both DLEU2 and the control, as documented by BrdU incorporation assays. Thus, expression of the miR-15a/16-1 cluster seems to control cellular proliferation, possibly by inhibiting the G0/G1 phase transition. Altogether, the results of the knockout and re-expression experiments suggest that the miR-15a/16-1 cluster exhibits negative control of proliferation both in human and mouse B cells. Conversely, the DLEU2 transcript per se did not affect proliferation of 13q14 homozygous deleted cells [56, 57]. Because their findings suggested that miR-15a/16-1 may affect the G0/G1-S phase transition in B cells, the authors sought to identify candidate G0/G1-S phase-related genes among inferred miR-15a/16-1 targets predicted by different computational target prediction algorithms. Seven proteins (cyclins Ccnd2, Ccnd3, and Ccne1, and cyclin-dependent kinases Cdk4, Cdk6, Chk1, and Mcm5) known to be involved in the regulation of the G0/G1-S phase transition, were downregulated in I83E95 13q14−/− cells
