MicroRNA-34a(miR-34a), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as a tumor suppressor microRNA. However, the profile and biological effects of miR-34a in breast cancer are still unclear. In this study, we aimed to determine the effect of miR-34a on the growth of breast cancer and to investigate whether its effect is achieved by targeting Bcl-2 and SIRT1. We examined miR-34a levels in breast cancer cell lines and breast cancer specimens by qRT-PCR. Proliferation assay, apoptosis assay, and morphological monitoring were performed to assess the tumor suppression effect of miR-34a in breast cancer cell lines. Western blotting was used to identify the targets of miR-34a. We also investigated the anti-tumor effects of the treatment combining miR-34a with 5-FU in breast cancer cells. We found that miR-34a expression was down-regulated in 5 breast cancer cell lines compared with the immortalized normal mammary epithelial cell line 184A1, and was also down-regulated by almost 50 % in breast cancer samples compared with their corresponding adjacent non-malignant breast tissues. Ectopic restoration of miR-34a in breast cancer cells suppressed cells proliferation, invasion, and induced apoptosis. Bcl-2 and SIRT1 as the targets of miR-34a were found to be in reverse correlation with ectopic expression of miR-34a. Furthermore, the treatment combining miR-34a with 5-FU significantly showed more efficient anti-tumor effects than single treatment of miR-34a or 5-FU. Since miR-34a functions as tumor suppressor microRNA in breast cancer, modulating miR-34a level in breast cancer was suggested to be a new and useful approach of breast cancer therapy.

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Purpose: The purpose of this study was to investigate the clinicopathologic significance and potential role of miR-200b and miR-200c

BackgroundMicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.MethodsThe expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.ResultsWe found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.ConclusionsOur study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.

The activator protein 1 (AP-1) transcription factor c-Jun is crucial for neuronal apoptosis. However, c-Jun dimerization partners and the regulation of these proteins in neuronal apoptosis remain unknown. Here we report that c-Jun-mediated neuronal apoptosis requires the concomitant activation of activating transcription factor-2 (ATF2) and downregulation of c-Fos. Furthermore, we have observed that c-Jun predominantly heterodimerizes with ATF2 and that the c-Jun/ATF2 complex promotes apoptosis by triggering ATF activity. Inhibition of c-Jun/ATF2 heterodimerization using dominant negative mutants, small hairpin RNAs, or decoy oligonucleotides was able to rescue neurons from apoptosis, whereas constitutively active ATF2 and c-Jun mutants were found to synergistically stimulate apoptosis.