Thus, as potential regulators in the termination stage of LR, the specific roles and mechanisms of these factors remain to be elucidated. MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation, by targeting different genes. Recently, some studies have described the roles of miRNAs in the process of LR. For instance, miR-21 expression was up-regulated during the early phases of LR, which inhibits Peli1 and potentially regulate NF-kB signaling ; miR-23b was down-regulated in the termination phase of LR, and may contribute to activation of the TGF-b1/Smad3 signaling. Thus, analysis about microRNA and related target genes may provide unique insights into the ��stop�� signal of LR and hepatocyte proliferation. In the present study, we mainly focused on miR-34a based on its expression pattern after PHx and its antiproliferative function in rat hepatocytes, along with its target genes. Our data suggests that miR-34a might also be a potential ��stop�� signal that contributes to the suppression of hepatocyte proliferation during the late phase of LR. Despite strong evidence that miRNAs are involved in the priming and progression phase of LR, little is known about how miRNAs affect the termination stage. To gain more insights into the roles of miRNAs, we performed a miRNA microarray analysis on late-phase regenerating livers. MiR-34a with,6-fold change was identified by microarray and qRT-PCR. Intriguingly, miR-34a is well known for its anti-oncogenic activity in several cancers, including hepatocellular carcinoma. Therefore, we hypothesized that miR-34a was a key suppressor of hepatocyte proliferation and might be a negative regulator during LR, like other ��stop�� signals as TGF-b and activins. To confirm the role of miR-34a in normal hepatocytes, we used cultured rat liver cells as cell models. Our data showed that miR-34a drastically inhibited BRL-3A cell growth and induced a significant G2/M arrest. However, in previous study, ectopic miR-34a was shown to induce a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. We assumed that the discrepancy may be caused by the different backgrounds and molecular mechanisms between normal cells and tumor cells. For instance, in tumor cells, the aberrant activated E2F complexes can work on the target genes whose products regulate the G1/S transition; and loss of regulation at the G1/S transition appears to be a common event among virtually all types of human tumor. Moreover, our data were also supported by a recent study of Factor, who discovered that c-Met deficient hepatocytes were blocked in early/ mid G2 phase. To determine how miR-34a influences the hepatocyte proliferation, we then used a Molecular Annotation System to categorize all putative target genes of miR-34a predicted by Targetscan.