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.

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.

Recurrence and metastasis result in a poor prognosis for breast cancer patients. Recent studies have demonstrated that microRNAs (miRNAs) play vital roles in the development and metastasis of breast cancer. In this study, we investigated the therapeutic potential of miR-34a in breast cancer. We found that miR-34a is downregulated in breast cancer cell lines and tissues, compared with normal cell lines and the adjacent nontumor tissues, respectively. To explore the therapeutic potential of miR-34a, we designed a targeted miR-34a expression plasmid (T-VISA-miR-34a) using the T-VISA system, and evaluated its antitumor effects, efficacy, mechanism of action, and systemic toxicity. T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed breast cancer cell growth, migration, and invasion in vitro by downregulating the protein expression levels of the miR-34a target genes E2F3, CD44, and SIRT1. In an orthotopic mouse model of breast cancer, intravenous injection of T-VISA-miR-34a:liposomal complex nanoparticles significantly inhibited tumor growth, prolonged survival, and did not induce systemic toxicity. In conclusion, T-VISA-miR-34a lead to robust, specific overexpression of miR-34a in breast cancer cells and induced potent antitumor effects in vitro and in vivo. T-VISA-miR-34a may provide a potentially useful, specific, and safe-targeted therapeutic approach for breast cancer.

BackgroundHuman epididymis protein 4 (HE4), has recently been reported as a mediator of renal fibrosis. However, serum HE4 levels appear in a large number of patient samples with chronic kidney disease (CKD), and the relationship of these levels to disease severity and renal fibrosis is unknown.MethodsIn 427 patients at different stages of CKD excluding gynecologic cancer and 173 healthy subjects, serum HE4 concentrations were tested by chemiluminescent microparticle immunoassay. Renal biopsy was performed on 259 of 427 subjects. Histological findings were evaluated using standard immunohistochemistry.ResultsThe levels of serum HE4 were higher in CKD patients than in healthy subjects, and higher levels were associated with more severe CKD stages. Patients with more severe renal fibrosis tended to have higher HE4 levels, and correlation analysis showed a significant correlation between HE4 and degree of renal fibrosis (r = 0.938, P < 0.0001). HE4 can be a predictor of renal fibrosis in CKD patients; the area under the receiver-operating characteristic curve (AUC-ROC) was 0.99, higher than the AUC-ROC of serum creatinine (0.89).ConclusionElevated levels of serum HE4 are associated with decreased kidney function, and also with an advanced stage of renal fibrosis, suggesting that HE4 may serve as a valuable clinical biomarker for renal fibrosis of CKD.

Abstract. Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterized by the formation of calcium phosphate microliths in the alveoli. Mutations in the gene encoding the solute carrier family 34 member 2 gene are considered to be involved in the pathogenesis of PAM. Although PAM can develop in children, the majority of patients with PAM are diagnosed in adulthood due to the slow progressive nature of the disease within the lungs. In childhood, the majority of patients with PAM are asymptomatic and changes in the lung parenchyma are usually identified incidentally. Symptoms of PAM typically appear in the third or fourth decade of life and there is often a notable dissociation between the advanced radiological findings and the mild clinical presentation. A positive diagnosis of PAM is reached by the combination of a positive chest radiograph and histological examination. Genetic testing may help to identify other latent patients in the family of the patient with PAM. In the present study, the cases of 3 patients diagnosed with PAM have been reported, including their clinical presentation, radio imaging, pathological symptoms, genetic test results and treatment plans, as well as the associated literature.