ABSTRACT
MicroRNAs (miRNAs) expression aberration has been discovered in almost all human cancers, thus offering a group of potential diagnostic markers, prognostic factors and therapeutic targets in tumorigenesis. Now our data showed that miR-200c, which is downregulated in osteosarcoma tissues, drives chemosensitivity to cisplatin in osteosarcoma. We demonstrated that AKT2 is a direct target of miR-200c, Spearman's rank correlation analysis showed that the expression levels of AKT2 and miR-200c in 35 pairs of osteosarcoma specimens were inversely correlated. Moreover, miR-200c inhibited cell proliferation and cell migration. Taken together, for the first time, our results demonstrate that miR-200c plays a significant role in osteosarcoma tumor growth and chemosensitivity by regulating AKT2, which may provide a novel therapeutic strategy for treatment of osteosarcoma.
Subject(s)
Bone Neoplasms/pathology , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , MicroRNAs/metabolism , Osteosarcoma/pathology , Proto-Oncogene Proteins c-akt/metabolism , 3' Untranslated Regions , Animals , Antagomirs/metabolism , Apoptosis/drug effects , Bone Neoplasms/drug therapy , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cisplatin/therapeutic use , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Osteosarcoma/drug therapy , Osteosarcoma/metabolism , Proto-Oncogene Proteins c-akt/chemistry , Proto-Oncogene Proteins c-akt/genetics , Transplantation, HeterologousABSTRACT
MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level. MicroRNAs play an important role in the development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-100 was downregulated in many cancers; however, the role of miR-100 in human osteosarcoma has not been totally elucidated. In this study, we demonstrate that the expression of miR-100 was significantly downregulated in human osteosarcoma tissues compared to the adjacent tissues. Enforced expression of miR-100 inhibited cell proliferation, migration, and invasion abilities of osteosarcoma cells, U-2OS, and MG-63. Additionally, miR-100 also sensitized osteosarcoma cells to cisplatin and promoted apoptosis. Furthermore, overexpression of miR-100 decreased the expression of insulin-like growth factor I receptor and inhibited PI3K/AKT and MAPK/ERK signaling. In human clinical specimens, insulin-like growth factor I receptor was inversely correlated with miR-100 in osteosarcoma tissues. Collectively, our results demonstrate that miR-100 is a tumor suppressor microRNA and indicate its potential application for the treatment of osteosarcoma in future.
