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

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.