Abstract
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3′-untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.
Highlights
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and contributes to 8.9% of cancer mortality among children [1–3]
Shen et al revealed that AKT activation by long noncoding RNA lncARSR conferred chemoresistance to adriamycin and facilitated osteosarcoma progression [13]
Cells were incubated with the mimic, inhibitor of miR-181a-5p, or their negative control (NC) at a concentration of 100 nmol/L for 24 h using Lipofectamine 6000 reagent (Beyotime; Shanghai, China), and cultured in fresh medium supplemented with 10% fetal bovine serum (FBS) for additional 96 h [29]. miR-181a-5p mimic, inhibitor, and the NC were all purchased from Guangzhou RiboBio Co., Ltd. (Guangzhou, China)
Summary
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and contributes to 8.9% of cancer mortality among children [1–3]. Shen et al revealed that AKT activation by long noncoding RNA lncARSR conferred chemoresistance to adriamycin and facilitated osteosarcoma progression [13]. AKT inhibition significantly suppressed osteosarcoma cell proliferation and the malignant phenotype [14, 15]. It is well-accepted that AKT is primarily dephosphorylated and inactivated by phosphatase and tensin homolog deleted on chromosome ten (PTEN), a major tumor suppressor gene in humans [16–18]. Inhibiting PTEN activity was capable of promoting osteosarcoma progression through activating AKT pathway [19]. Based on these findings, it is reasonable to target PTEN/ AKT pathway for the treatment of osteosarcoma. We aim to investigate the function and potential molecular basis of miR-181a-5p in osteosarcoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
