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miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14
- Source :
- Cell Death & Disease
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3′-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan–Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinogenesis
Transplantation, Heterologous
Immunology
Bone Neoplasms
Kaplan-Meier Estimate
Biology
medicine.disease_cause
Bioinformatics
Metastasis
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Cell Movement
Cyclin-dependent kinase
Cell Line, Tumor
microRNA
medicine
Animals
Humans
Neoplasm Invasiveness
Epigenetics
Neoplasm Metastasis
3' Untranslated Regions
Cell Proliferation
Regulation of gene expression
Mice, Inbred BALB C
Osteosarcoma
Binding Sites
Cell growth
Cell Biology
medicine.disease
Cyclin-Dependent Kinases
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Original Article
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....53871049708747c759c60d89225f3485