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Dysregulation of microRNA-106a-5p-RUNX1 axis associates with clinical progression and prognosis of osteosarcoma patients
- Source :
- Pathology - Research and Practice. 215:152686
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- MicroRNA-106a-5p (miR-106a-5p) functions as a tumor suppressor in osteosarcoma cells. Here, we aimed to identify novel target genes of miR-106a-5p in osteosarcoma, as well as to investigate their prognostic value and the biological functions. At first, the mammalian runt-related factor 1 (RUNX1) was identified as one of the target genes of miR-106a-5p in osteosarcoma cells by luciferase reporter gene assay, real-time quantitative RT-PCR and Western blot analysis. Then, the expression levels of miR-106a-5p and RUNX1 in osteosarcoma tissues were detected, and their associations with clinicopathological features and patients' prognosis were statistically analyzed. Compared with adjacent non-cancerous tissues, miR-106a-5p and RUNX1 mRNA/protein expression in osteosarcoma tissues were significantly decreased and increased, respectively (all P 0.01). Low miR-106a-5p, high RUNX1 and miR-106a-5p-low/RUNX1-high expression in osteosarcoma tissues were all significantly associated with advanced Enneking stage, positive metastasis and shorter overall survival (all P 0.05). Moreover, miR-106a-5p and RUNX1 expression, alone or in combination, were identified as independent prognostic factors for osteosarcoma patients' overall survival. Functionally, the enforced expression of miR-106a-5p significantly suppressed proliferation and invasion of osteosarcoma cells, while the overexpression of RUNX1 effectively reversed its suppressive roles. In conclusion, our findings show the dysregulation of miR-106a-5p-RUNX1 axis in human osteosarcoma tissues and suggest its crucial roles in cancer progression and patients' prognosis. More interestingly, miR-106a-5p may function as a tumor suppressor in osteosarcoma cells via regulating its target gene RUNX1.
- Subjects :
- Adult
Male
musculoskeletal diseases
0301 basic medicine
Adolescent
Bone Neoplasms
Pathology and Forensic Medicine
law.invention
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Western blot
Cell Movement
law
Cell Line, Tumor
microRNA
Humans
Medicine
Neoplasm Invasiveness
Child
Gene
Cell Proliferation
Neoplasm Staging
Osteosarcoma
Messenger RNA
medicine.diagnostic_test
business.industry
Cell Biology
Middle Aged
medicine.disease
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
RUNX1
chemistry
030220 oncology & carcinogenesis
Core Binding Factor Alpha 2 Subunit
Cancer research
Suppressor
Female
business
Clinical progression
Signal Transduction
Subjects
Details
- ISSN :
- 03440338
- Volume :
- 215
- Database :
- OpenAIRE
- Journal :
- Pathology - Research and Practice
- Accession number :
- edsair.doi.dedup.....ad6513751c07f2b4bc6e3bfd514f0217