MiR-185-3p downregulates advanced glycosylation end product receptor expression and improves renal function in diabetic nephropathy mice.

OBJECTIVE: To investigate the effects of the downregulation of AGER by miRNA-185-3p on renal function in diabetic nephropathy (DN) mice. MATERIALS AND METHODS: Mice were divided into normal, model, NC, miR-185-3p mimic, si-AGER, and miR-185-3p mimic + si-AGER groups. Eight weeks following the establishment of the model, various indicators were assessed. RESULTS: Compared to control groups, miR-185-3p expression, body weight, superoxide dismutase (SOD) content, catalase (CAT) content, proliferation, S-phase ratios, and proliferating cell nuclear antigen (PCNA) expression were significantly lower in all experimental groups, whilst AGER expression, water intake, food intake, urine volume, urine protein content, serum creatinine (Scr), Blood Urea Nitrogen (BUN), MDA content, G0/G1 status, and rates of apoptosis were significantly higher (all p<0.05). Compared to the model group, miR-185-3p mimics, si-AGER, and miR-185-3p mimic + si-AGER groups had a significantly higher SOD content, CAT content, proliferation, S phase ratios, PCNA expression and lower AGER expression, water intake, food intake, urine output, urine protein, Scr, BUN, MDA content, G0/G1 ratios, and apoptosis rates (all p<0.05). In addition, the effects of the miR-185-3p mimics + si-AGER were superior to miR-185-3p mimics and si-AGER monotherapy groups (both p<0.05). CONCLUSIONS: MiR-185-3p inhibits AGER, downregulates AGER expression, and improves renal function in DN mice.

MicroRNAs in gastric cancer: from bench to bedside.

Gastric carcinogenesis results from complex interactions between host and environmental and bacterial factors, and this leads to genetic and epigenetic deregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate almost 30% of human genes post transcriptionally and they are crucial in the initiation and progression of various diseases; especially malignancies. Accumulated evidence documents changes in gene sequences and epigenetic modifications. These then lead to abnormal miRNA expression in gastric cancer (GC) and also to deregulated miRNAs which act as oncogenes or tumor suppressors by regulating related target genes and contributing to malignant phenotypes. This altered miRNA expression in body fluids could well provide a novel biomarker for GC patient diagnosis and prognosis. MiRNAs present a promising target for GC treatment, and more tempting, for eradication of gastric cancer stem cells. This latter sub-group of tumor cells is thought to initiate and maintain GC development. Herein, we review the aberrant expression of miRNA expression and the underlying mechanisms and consequential effects of miRNA de-regulation. This identifies the responsible gastric cancer target genes, and highlights potential clinical applications.

Down-regulation of TSG101 by small interfering RNA inhibits the proliferation of breast cancer cells through the MAPK/ERK signal pathway.

We designed to investigate the effects of down-regulating the tumor susceptibility gene 101 (TSG101) on the proliferation and apoptosis of the human breast cancer MCF-7 cell line, and the role of the MAPK/ERK signal pathway in this process. The siRNA against TSG101 was transfected into the breast cancer MCF-7 cell line using Lipofectamine 2000. After TSG101 knockdown, the proliferation of MCF-7 cells was measured by the MTT assay. The cell cycle distribution and apoptosis were examined by using flow cytometry while cell migration was measured using a transwell assay. The protein level of p-ERK was further assessed by immunofluorescence and western blotting. Our results are as following, the MCF-7 cells transfected with TSG101 siRNA proliferated significantly slower and exhibited significantly increased rates of apoptosis compared to the control cells. In the TSG101 siRNA transfected cells, the percentage of cells in the G0/G1 and S phase of the cell cycle was significantly higher and lower, respectively, compared to the control cells. Moreover, the migration ability of TSG101 siRNA transfected cells was lower than the control groups. Lastly, the level of p-ERK protein in TSG101 siRNA transfected cells was significantly decreased compared with the control cells. In conclusion, TSG101 knockdown in breast cancer cells induces apoptosis and inhibits proliferation. The TSG101 depleted cells are arrested at the G1/S transition of the cell cycle. The migration of breast cancer cells is also impaired by TSG101 siRNA. TSG101 may play a biological role through modulation of the MAPK/ERK signaling pathway in breast cancer.