Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma

H. Song, Z.-X. Bian, H.-Y. Li, Y. Zhang, J. Ma, S.-H. Chen, J.-B. Zhu, X. Zhang, J. Wang, S. Gu, M. Xu, Q.-H. Pan, M.-Z. Yin, L. Zheng

Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China. panqiuhui@scmc.com.cn

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• Oncology

OBJECTIVE: Various studies have shown that aberrant expression of circular RNAs (circRNAs) has a pivotal role in multifarious cancers. However, the role of circRNAs in hepatoblastoma (HB) is not clearly understood. In the present study, we attempted to explore the underlying mechanism of hsa_cric_0000594 in HB along with its clinical importance.

PATIENTS AND METHODS: In our research, the expression pattern of hsa_circ_0000594 in HB tissues and matched normal liver tissues was determined by in situ hybridization and RT-qPCR. Proliferation, viability, migration, and apoptosis of HB cell lines were detected via Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays. The interaction of hsa_circ_0000594 with miR-217 was investigated by Dual-Luciferase reporter assay.

RESULTS: Expression levels of hsa_circ_0000594 were significantly upregulated in HB tissues compared with those in paired normal liver tissues and showed a clear association with the subtype of HB. The knockdown of hsa_circ_0000594 inhibited the malignant phenotype of HB. Bioinformatics analysis suggests that sirtuin 1 (SIRT1) may serve as a target gene of miR-217.

CONCLUSIONS: Mechanically, hsa_circ_0000594 was identified to have a critical role in HB development through the hsa_circ_0000594/mir-217/SIRT1 regulatory axis, which might become a novel diagnostic marker and potential therapeutic target in HB.

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