Abstract
Background: We have previously found that circ0085539/miR-526b-5p axis participated in the progression of osteosarcoma (OS). We have been interested in expanding the networking involving circ0085539 and miR-526-5p. We identified another critical downstream target of this axis, pleckstrin homology-like domain family A member 1 (PHLDA1), thus intending to uncover the interaction between the axis and PHLDA1.Methods: Live imaging of mice tumor xenografts was conducted. Immunohistochemistry (IHC) and H&E staining were performed for our in vivo experiment, while the CCK-8 assay, flow cytometry, wound healing, Transwell invasion, and clone formation were employed to assess cellular biological functions.Results: Circ0085539 was first found to be upregulated in osteosarcoma tissues and cell lines, and circ0085539 knockdown obviously suppressed proliferation and induced apoptosis. Subsequently, miR-526b-5p functionally attenuated the tumor suppressive effects induced by circ0106714 silencing on OS cells. PHLDA1 silencing significantly led to proliferation suppression, apoptosis induction, as well as the inhibition of migration, invasion, and colony formation capabilities in OS cells, which also could be restored by the miR-526b-5p inhibitor.Conclusion: Taken together, circ0085539 effectively promoted progression of osteosarcoma through sponging miR-526b-5p to release PHLDA1, strongly suggesting that in vivo intervention of circ0085539–miR-526b-5p–PHLDA1 axis could function as a promising OS-targeted therapy.
Highlights
Osteosarcoma (OS), derived from mesenchymal cells, has been reported to basically have its onset in adolescents [1]
We found that circ0085539 is one of the PVT1-encoded circular RNAs and is predicted to sponge miR-526b-5p
We found that since 2014, there have been approximately 10 studies related to the role of miR-526b in cancer, and 2 of them reported the downregulation of miR-526b-5p in oral squamous cell carcinoma and esophageal squamous cell carcinoma as well as its tumor suppressive effect, respectively
Summary
Osteosarcoma (OS), derived from mesenchymal cells, has been reported to basically have its onset in adolescents [1]. The quality of life in adolescents is severely compromised by OS due to the disruption of bone development [2]. Circ0085539/ miR-526b-5p/ PHLDA1 in Osteosarcoma survival rate has not been effectively improved [3]. We have previously found that circ0085539/miR-526b-5p axis participated in the progression of osteosarcoma (OS). We have been interested in expanding the networking involving circ0085539 and miR-526-5p. We identified another critical downstream target of this axis, pleckstrin homology-like domain family A member 1 (PHLDA1), intending to uncover the interaction between the axis and PHLDA1
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