Abstract
Osteosarcoma is the most common primary bone tumour. Increasing evidence has demonstrated the pathogenic role of microRNA (miRNAs) dysregulation in tumour development. miR‐379 was previously reported to function as an oncogenic or tumour‐suppressing miRNA in a tissue‐dependent manner. However, its function in osteosarcoma remains unknown. In this study, we found that the expression of miR‐379 was downregulated in osteosarcoma tissues and cell lines. Further functional characterization revealed that miR‐379 suppressed osteosarcoma cell proliferation and invasion in vitro and retarded the growth of osteosarcoma xenografts in vivo. Mechanistically, PDK1 was identified as the direct target of miR‐379 in osteosarcoma, in which PDK1 expression was up‐regulated and showed inverse correlation with miR‐379. Enforced expression of PDK1 promoted osteosarcoma cell proliferation and rescued the anti‐proliferative effect of miR‐379. These data suggest that miR‐379 could function as a tumour‐suppressing miRNA via targeting PDK1 in osteosarcoma.
Highlights
Osteosarcoma is the most common primary tumour of bone with an incidence of 4–5 cases per million in young adults and adolescents [1,2,3,4]
We found that miR-379 expression was downregulated in osteosarcoma tissues and cell lines
The expression of miR-379 was downregulated in osteosarcoma tissues compared with their adjacent non-cancerous tissues (Fig. 1A)
Summary
Osteosarcoma is the most common primary tumour of bone with an incidence of 4–5 cases per million in young adults and adolescents [1,2,3,4]. Because of the advancement of its treatment, including surgery and multi-agent chemotherapy, the 5-year survival rate in patients with primary osteosarcoma has improved over the past several decades [5,6,7,8]. Several studies have demonstrated abnormal expression of miRNAs in different types of cancer, including gastric cancer, hepatocellular carcinoma, glioblastoma, ovarian carcinoma, breast cancer and laryngeal cancer [17,18,19,20,21,22]. It has been demonstrated that miR-379 expression was elevated in bone-metastatic prostate cancer cell lines and tissues. The expression of miR-379 was correlated with shortened progression-free survival of patients with prostate cancer [32]. Treatment with miR-379 inhibitor decreased bone metastasis and increased survival of mice transplanted with bone metastatic ARCaPM prostate cancer cells [32].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
