ABSTRACT
Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.
Subject(s)
MicroRNAs/metabolism , Multiple Myeloma/pathology , Proto-Oncogene Proteins c-raf/metabolism , Animals , Antagomirs/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Humans , MAP Kinase Signaling System , Male , Mice , Mice, Nude , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Middle Aged , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Multiple Myeloma/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-raf/antagonists & inhibitors , Proto-Oncogene Proteins c-raf/genetics , RNA Interference , RNA, Small Interfering/metabolismABSTRACT
OBJECTIVE: To evaluate indications and clinical results of total hip arthroplasties for degenerative hips with history of infection. METHODS: Seven cases of degenerative hip with history of infection underwent primary total hip arthroplasties, which involved 5 males and 2 females, with an average age of 45.8 years (range, 30 to 65 years). The quiescent period of infection were more than 10 years in all hips. According to Kim classification, 3 cases were of type I, and 4 of type II. The method to exclude active infection at the site of degenerative hips preoperatively was combination of physical examination, erythrocyte sedimentation rate and C-reactive protein level. The lateral incision was adopted in all cases, and all prosthesis were cementless. The clinical results of affected hips were assessed according to Harris hip score. RESULTS: The follow-up was performed with the mean duration of 33.5 months (range, 21 to 44 months). No recurrence of infection, damage of nerve function or deep vein thrombosis of lower extremities occurred in all cases. The mean Harris hip scores improved from 44.5 points preoperatively to 84 points at the latest follow-up. No aseptic loosening of prosthesis or periprosthetic osteolysis were found at the latest follow-up. CONCLUSION: Total hip arthroplasties has good short term results for degenerative hips with history of infection. It is important to select indicated cases and rule out the possibility of active infection.
