As described earlier, the function of Mir-29a in tumorigenesis and metastasis remains controversial. Muniyappa
et al. showed that Mir-29a was down-regulated in invasive lung cancer cells and invasive phenotype of cancer cells could be suppressed by ectopic expression of Mir-29a [
23]. Study from Xu et al. also showed that expression level of Mir-29a is significantly lower in various solid tumors [
24]. In contrast, Mir-29a is also shown to be up-regulated in certain leukemia cells [
25]. In this study, we focused on the role of Mir-29a in breast cancers cells. We showed that expression level of Mir-29a is down-regulated in various breast cancer cells (Figure
2). This data indicates that Mir-29a expression is probably associated with breast cancer. One piece of evidence to support this hypothesis is that over-expression of Mir-29a in breast cancer cells significantly reduce cancer cell growth rate (Figure
3B). Consistent with this result, knockdown of Mir-29a in normal mammary epithelial cells cause higher cell growth rate (Figure
4B). These data strongly suggested Mir-29a inhibited tumorigeneses through suppression of cell growth. We also showed that the inhibitory effect of Mir-29a to breast cancer cells is probably due to its role in arresting cells in G0/G1 cells (Figure
3C-E and
4C-E). Previous studies showed that Mir-29a is able to suppress the expression of tristetraprolin, which is involved in epithelial-to-mesenchymal transition [
17]. A study also showed that Mir-29a targets protein P42.3, which was also found, associated with tumorigenicity [
26]. In this study, we showed that Mir-29a negatively regulated expression of B-Myb (Figure
5), which is a transcription factor broadly involved in regulating cell cycle and apoptosis and probably is a promoting factor for cancer [
27]. Downstream effectors of B-Myb, such as Cyclin A2 and D1, were also correspondingly regulated by Mir-29a. Cyclin D1 is one of highly over-expressed proteins in breast cancer cells and over-expression of Cyclin D1 protein was found in 40-90% of cases of invasive breast cancer [
28]. Cyclin A2 is involved in S phase and G2-M phase transition and is also over-expressed in various cancers [
29‐
31]. Taken together, in current paper, we showed that Mir-29a may act as a tumor suppressor through its inhibitory function on growth of breast cancer cells, and down-regulating expression of B-Myb by Mir-29a may contribute to this process.