Circ0085539 Promotes Osteosarcoma Progression by Suppressing miR-526b-5p and PHLDA1 Axis

Pengcheng Liu; Wei Liu; Hang Gao; Yuanding Zhang; Ming Yan; Xu Wang

doi:10.3389/fonc.2020.01250

Circ0085539 Promotes Osteosarcoma Progression by Suppressing miR-526b-5p and PHLDA1 Axis

Front Oncol. 2020 Aug 26:10:1250. doi: 10.3389/fonc.2020.01250. eCollection 2020.

Authors

Pengcheng Liu¹, Wei Liu², Hang Gao³, Yuanding Zhang⁴, Ming Yan², Xu Wang⁵

Affiliations

¹ Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun City, China.
² Department of Spine Surgery, The First Hospital of Jilin University, Changchun City, China.
³ Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun City, China.
⁴ Department of Otolaryngology Head and Neck Surgery, The First Hospital of Jilin University, Changchun City, China.
⁵ Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun City, China.

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.

Keywords: PHLDA1; circ0085539; miR-526b-5p; oncogene; osteosarcoma.