MiR-486-5p inhibits IL-22-induced epithelial-mesenchymal transition of breast cancer cell by repressing Dock1.

Epithelial-mesenchymal transition (EMT) is one of important steps that lead to cancer metastasis. Interleukin-22 (IL-22) is a T helper 17 (Th17) cells-secreted cytokine, it can promote invasion and metastasis of many cancers. MiR-486-5p is a microRNA that known to function as a tumor suppressor, and bioinformatics analysis predicts that Dock-1 has a binding site of miR-486-5p. In current research, we examined the relative expression levels of miR-486-5p and Dock-1 in 80 pairs of breast cancer tissues and corresponding adjacent normal tissues, also the effects of modifying their levels in cultured cells. We illustrated that IL-22 and Dock1 promote the invasion, metastasis, and EMT of breast cancer using Transwell invasion assay, western blot and immunofluorescence. MiR-486-5p directly bound the Dock1 mRNA 3' untranslated region and inhibited IL-22-induced EMT of breast cancer cells via the Dock1/NF-κB/Snail signaling pathway. Dock1 overexpression reversed the effect caused by the overexpression of miR-486-5p. Overexpression of miR-486-5p or downregulation of Dock1 reduced pulmonary metastasis in mice. This study provided insight into a potential mechanism where miRNAs regulate breast cancer metastasis and provided a novel therapeutic target for breast cancer treatment.

Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. This study was designed to investigate the potential of Ribosomal Protein L22-like1 (RPL22L1) and Ribosomal Protein S21 (RPS21) as diagnostic and prognostic biomarkers for PCa. First, RPL22L1 and RPS21 were screened as the key molecular of PCa by bioinformatics analysis. Subsequently, the prostate tissue samples were stained for antibodies against RPL22L1 and RPS21. The unbiased signal quantification was performed by ImageJ software, and the results showed that the expression of RPL22L1 and RPS21 exhibited significant differences between the PCa tissues and the normal prostate tissues. Receiver-operating characteristics (ROC) curves were prepared, and then the area under the curve (AUC) values of RPL22L1 and RPS21 were calculated as 0.798 and 0.768, and the likelihood ratio (LR) values of RPL22L1 and RPS21 were calculated as 2.86 and 2.53. These data implied that the over-expression of RPL22L1 and RPS21 is associated with the presence of PCa. The further analysis suggested that the expression of RPL22L1 and RPS21 were significantly higher in high Gleason grade than they were in low Gleason grade. In addition, in vitro studies were undertaken to evaluate the roles of RPL22L1 and RPS21 in PCa. The results revealed that these genes promote PCa cell proliferation, migration and invasion, and inhibit PCa cell apoptosis. Taken together, these data showed that RPL22L1 and RPS21 exhibited higher expression in human prostate cancer tissue, and involved in PCa cell proliferation and invasion. This research provided a novel insight into diagnostic and prognostic biomarkers for PCa.

MiR-577 suppresses epithelial-mesenchymal transition and metastasis of breast cancer by targeting Rab25.

BACKGROUND: MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR-577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR-577 on breast cancer (BC). METHODS: The relative level of miR-577 in 120 BC tissues and cells was detected by real-time PCR. MDA-MB-231 cells with upregulated miR-577 and MCF-7 cells with downregulated miR-577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial-mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR-577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR-577 on BC metastasis. RESULTS: MiR-577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR-577 expression. Moreover, miR-577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR-577 directly regulated Rab25 in BC. Rab25 upregulation by miR-577 decreased the levels of E-cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR-577 in BC. CONCLUSION: Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in BC. MiR-577 and Rab25 are considered potential targets of BC treatment.

Association between estimated glomerular filtration rate, ankle-brachial index, and recurrent ischemic stroke in a Chinese population of ischemic stroke patients.

BACKGROUND: Very few studies have examined combined association of estimated glomerular filtration rate (eGFR) and ankle-brachial index (ABI) on recurrent ischemic stroke in patients with ischemic stroke in Chinese populations. PATIENTS AND METHODS: A Chinese population of 1219 ischemic stroke patients was followed up in this six-year prospective study. RESULTS: 1080 ischemic stroke patients with complete follow-up data were included in the statistical analysis. A total of 245 ischemic stroke patients (22.7 %) had recurrent ischemic stroke during follow-up. The Incidence of recurrent ischemic stroke was significantly increased with decreasing eGFR levels and that of patients with eGFR < 30 ml/min/1.73m2 was the highest. Hazard ratio (HR) of eGFR < 30 ml/min/1.73m2 to recurrent ischemic stroke was 2.633 (95 % CI: 1.653 - 4.194) compared with that of eGFR ≥ 60 ml/min/1.73m2 after adjusting for other potential confounders using Cox regression analysis. Incidence of recurrent ischemic stroke was significantly increased with simultaneously decreasing eGFR and ABI. The highest percentage (71.4 %) of patients with eGFR < 30 ml/min/1.73m2 and ABI ≤ 0.4 simultaneously had recurrent ischemic stroke during follow-up. HR of eGFR < 30 ml/min/1.73m2 and ABI ≤ 0.4 simultaneously with recurrent ischemic stroke was 9.415 (95 % CI: 3.479 - 25.483) compared with that of eGFR ≥ 60 ml/min/1.73m2 and ABI > 1.0 to ≤ 1.4 respectively CONCLUSIONS: Low ABI and low eGFR together had synergistic effects on increasing recurrent ischemic stroke of ischemic stroke patients during a long-term follow-up.

Predictive value of ankle-brachial index to all-cause mortality and cardiovascular mortality in Chinese patients with chronic kidney disease.

BACKGROUND: To investigate the predictive value of ankle-brachial index (ABI) for all-cause mortality and cardiovascular mortality in Chinese patients with chronic kidney disease (CKD). PATIENTS AND METHODS: 1563 CKD patients were enrolled in the cohort and were followed up for about 3 years in China. CKD was defined as an eGFR less than 60 ml/min/1.73m(2). 573 participants were diagnosed with PAD using ABI <= 0.90. Their average age was 73.4 ±8.2 years. RESULTS: During a median follow-up of 38 months, there were 1353 CKD patients with complete data. A total of 313 patients (161 with and 152 without PAD) died during follow-up. 184 deaths (99 with and 85 without PAD) were caused by cardiovascular disease (CVD). All-cause and CVD mortality of CKD patients with PAD was increased 2.2-fold and 2.4-fold compared with CKD patients without PAD. The hazard ratio (HR) of PAD for all-cause and CVD mortality was 2.15 (95 % CI: 1.66 - 2.79) and 2.51 (95 % CI: 1.80 - 3.50) respectively. Mortality of CKD patients significantly increased with decreasing ABI. That of CKD patients with ABI <= 0.4 was the highest (42.9 % and 28.6 %, respectively) in different ABI categories. Relative risks of all-cause and CVD mortality of CKD patients with ABI <= 0.4 were increased 3.479-fold (95 % CI: 2.076 - 5.830) and 4.960-fold (95 % CI: 2.644 - 9.302) respectively compared with those of patients with ABI > 1.0 and <= 1.4. Special models to evaluate the predictive value of ABI to mortality of CKD patients suggested that addition of ABI significantly increased the predictive value of the model for 3-year mortality compared with a model including conventional risk factors alone. CONCLUSIONS: Low ankle-brachial index can predict increased mortality of chronic kidney disease patients. Addition of ankle-brachial index can significantly improve the prediction of 3-year mortality compared with conventional risk factors alone.