MicroRNA499a5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling
A number of studies have attempted to elucidate the association between mircoRNAs (miRNAs/miRs) and cancerassociated processes. The aim of the present study was to determine how miR499a5p intervenes in human osteosarcoma cell proliferation and differentiation. The cancerous tissues
and adjacent noncancerous tissues of 62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis revealed that 29 miRNAs were upregulated while 26 were downregulated, among which miR499a5p expression was the most decreased. Western blot analysis and reverse transcriptionquantitative
polymerase chain reaction demonstrated that the mRNA and protein expression of miR499a5p was lower, while that of protein phosphatase 1D (PPM1D) was higher in OS tissues compared with expression levels in normal tissues. Furthermore, miR499a5p expression was markedly decreased in the metastatic
tumors and in those at stage III+IV compared with the nonmetastatic tumors and those at stage I, respectively. In addition, following transfection of the human OS MG63 cell line with an miR499a5p mimic, the expression of miR499a5p was elevated while the protein and mRNA expression
of PPM1D was decreased. When combining these findings with the information obtained from the Targetscan predictive software, it was confirmed that PPM1D was targeted by miR499a5p. In MG63 cells transfected with an miR499a5p mimic, PPM1Dassociated downstream proteins phosphorylated protein
kinase B (pAkt) and phosphorylated glycogen synthase kinase 3β (pGSK3β) were significantly downregulated compared with the negative control (NC) group, while the expression of pAkt and pGSK3β were significantly elevated in the tumor tissues compared with the adjacent nontumor
tissues. Simultaneously, the growth and proliferation activity of MG63 cells were notably reduced when transfected with the miR499a5p mimic, compared with the NC group. Therefore, it may be concluded that miR499a5p suppresses OS cell proliferation and differentiation by targeting PPM1D through
modulation of Akt/GSK3β signaling.
Document Type: Research Article
Affiliations: 1: Department of Hand and Foot Surgery and Reparative and Reconstructive Surgery, Orthopedic Hospital of The Second Hospital of Jilin University, Changchun, Jilin 130000, P.R. China 2: Department of Burns, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China 3: Department of Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710054, P.R. China 4: Department of Orthopedics, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710054, P.R. China
Publication date: 01 April 2018
- Oncology Letters is a monthly, peer-reviewed journal, available in print and online, that focuses on all aspects of clinical oncology, as well as in vitro and in vivo experimental model systems relevant to the mechanisms of disease.
The principal aim of Oncology Letters is to provide the prompt publication of original studies of high quality that pertain to clinical oncology, chemotherapy, oncogenes, carcinogenesis, metastasis, epidemiology and viral oncology in the form of original research, reviews and case reports. - Editorial Board
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