Hsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion

Junxu Yang; Zizhu Hu; Xiao Ru; Mingwei He; Ziwei Hu; Xiong Qin; Shihui Xiao; Dachang Liu; Hanji Huang; Qingjun Wei

doi:10.1016/j.gene.2025.149221

Hsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion

Gene. 2025 Jan 4:149221. doi: 10.1016/j.gene.2025.149221. Online ahead of print.

Authors

Junxu Yang¹, Zizhu Hu², Xiao Ru³, Mingwei He¹, Ziwei Hu³, Xiong Qin⁴, Shihui Xiao¹, Dachang Liu¹, Hanji Huang⁵, Qingjun Wei⁶

Affiliations

¹ Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi, PR China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi, PR China.
² Southern Medical University, 510000 Guangzhou, PR China.
³ Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi, PR China.
⁴ Department of Bone and Soft Tissue Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, PR China.
⁵ Department of Reproductive Medicine, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, Guangxi, PR China.
⁶ Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, No. 166 East University Road, Nanning 530005, Guangxi, PR China. Electronic address: [email protected].

PMID: 39761802
DOI: 10.1016/j.gene.2025.149221

Abstract

Emerging evidence suggests that circular RNAs (circRNAs), a class of non-coding RNAs, play a critical role in the progression of several cancers, including osteosarcoma (OS). In this study, we focused on a specific circRNA, hsa_circ_0002005, derived from the mesoderm-induced early response 1 family member 2 (MIER2) gene. We determined the expression levels of hsa_circ_0002005 in OS samples through the use of real-time quantitative polymerase chain reaction (RT-qPCR). To assess the effect of hsa_circ_0002005, we used lentiviral analysis and performed several assays including transwell migration, cell invasion, 5-ethynyl-2'-deoxyuridine assay (EdU), cell counting kit-8 (CCK-8), proliferation, colony formation, and western blotting. In addition, we investigated the delivery mechanism of hsa_circ_0002005 in nude mice and predicted the interaction network involving hsa_circ_0002005, microRNA (miRNA), and mRNAs through bioinformatics analysis. The results showed that hsa_circ_0002005 is overexpressed in OS tissues and cells and is derived from exons 2 to 7 of the MIER2 gene. Knockdown of hsa_circ_0002005 markedly reduced the proliferation, migration, and invasive capabilities of cells, as well as their metastatic potential. We discovered miRNAs that may engage with hsa_circ_0002005. Further mechanistic studies indicated that the suppression of hsa_circ_0002005 influenced the expression levels of proteins associated with the epithelial-mesenchymal transition (EMT), suggesting its regulatory role in EMT progression through modulation of cell proliferation, migration, and invasion.

Keywords: EMT; Hsa_circ_0002005; Metastasis; Migration; Osteosarcoma.