The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma

Zhiyi Wang; Zhenyuan Gao; Yi-Fei Yang; Bi Liu; Fei Yu; Hai-Ming Ye; Ming Lei; Xiaoming Wu

doi:10.1016/j.bone.2024.117333

The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma

Bone. 2024 Nov 18:117333. doi: 10.1016/j.bone.2024.117333. Online ahead of print.

Authors

Zhiyi Wang¹, Zhenyuan Gao², Yi-Fei Yang³, Bi Liu⁴, Fei Yu³, Hai-Ming Ye³, Ming Lei⁵, Xiaoming Wu⁶

Affiliations

¹ Department of Orthopedics, ShanXi Bethune Hospital, Taiyuan 030000, China.
² Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
³ Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China; National and Local Joint Engineering Research Center for Orthopedic Biomaterials, Shenzhen 518036, Guangdong, China; Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Shenzhen 518036, Guangdong, China.
⁴ Department of Orthopedics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China; The Second Clinical Medical College, Jinan University, Shenzhen 518020, Guangdong, China; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, China.
⁵ Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China; National and Local Joint Engineering Research Center for Orthopedic Biomaterials, Shenzhen 518036, Guangdong, China; Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Shenzhen 518036, Guangdong, China. Electronic address: doc_leiming@163.com.
⁶ Department of Orthopedics, Affiliated Hospital of Hebei University, Baoding 071000, China. Electronic address: Wuxiaominghb@126.com.

PMID: 39566705
DOI: 10.1016/j.bone.2024.117333

Abstract

Background: Osteosarcoma, as the most common primary malignant bone tumor, has become one of the main causes of cancer-related deaths in adolescents and children. This study thus proposes new biomarkers for OS based on whole-transcriptome re-analysis and experimental confirmation.

Methods: We find two circRNA dataset related to OS, from tissue and cell perspectives respectively, from the GEO database. Analysis of the tumor group and control group data used GEO2R, to obtain the differentially expressed (DE) circRNAs and take the intersection. The downstream miRNAs were predicted and subsequently the targeted mRNAs for these miRNAs were collected. These targeted mRNAs intersected with prognostic mRNAs reported in previous literature. CircRNA/miRNA/mRNA and circRNA/miRNA/mRNA/key pathway networks were constructed and GO and KEGG analyses were done. The prognostic values of hsa_circ_0032462, miR-488-3p, and SLC7A were confirmed in OS using Kaplan-Meier analyses and univariate/multivariate analyses. And the cellular functions of these three factors in OS were further explored through cell experiments.

Results: Five DEcircRNAs were obtained, targeting 42 miRNAs and linking 67 prognostic-related mRNA. GO analysis and KEGG analysis indicate that the mRNAs in the network were involved in various biological processes and signaling pathways related to OS. The luciferase report validated the targeting relationship of hsa_circ_0032462, miR-488-3p, and SLC7A. Cell survival, migration, and invasion experiments found that hsa_circ_0032462 and SLC7A promoted OS, while miR-488-3p inhibited OS.

Conclusion: Aberrantly expressed circRNAs in OS are involved in OS progression via the ceRNA network. hsa_circ_0032462-miR-488-3p-SLC7A1 axis can be developed to be alternative therapeutic targets for OS.

Keywords: CeRNA; Human osteosarcoma; Network; Prognosis; Therapeutic target; circRNA.