Bioinformatics Analysis of hsa_circ_0036683 Reveals its Potential Role in Hepatocellular Carcinoma
DOI:
https://doi.org/10.54097/8b7egd72Keywords:
Hepatocellular Carcinoma, Circular RNA, hsa_circ_0036683, ceRNA, BiomarkerAbstract
Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. Circular RNAs (circRNAs) exert crucial regulatory effects on HCC progression via the competing endogenous RNA (ceRNA) mechanism. As the potential role of hsa_circ_0036683 in HCC remains unclear, this study aimed to explore its expression characteristics and ceRNA regulatory mechanism in HCC through bioinformatics analysis. Methods: Differentially expressed circRNAs were identified from publicly available Gene Expression Omnibus (GEO) datasets. Furthermore, CircAtlas 3.0 was utilized to analyze the tissue expression, host gene expression pattern and cross-species conservation of hsa_circ_0036683. CircBank and CircInteractome were used to predict circRNA-miRNA interactions, and core miRNAs were screened via comprehensive evaluation of multiple binding indicators. TargetScan 8.0, miRTarBase and miRDB were applied to predict and screen overlapping target genes of the candidate miRNAs. Functional enrichment analyses, protein–protein interaction (PPI) networks were performed. Results: Bioinformatics analysis verified that hsa_circ_0036683 was significantly downregulated in HCC, with its expression positively correlated with the host gene, and presented high cross-species conservation. Eleven common miRNAs were obtained from two circRNA databases, and three core miRNAs (hsa-miR-591, hsa-miR-626, hsa-miR-630) were selected. Further target gene prediction yielded 7 overlapping genes for hsa-miR-591 and 9 for hsa-miR-630, while no common target was found for hsa-miR-626. GO and KEGG enrichment indicated involvement in transcriptional regulation, protein interaction, PI3K-Akt, HIF-1 and cancer-related signaling pathways. The PPI network analysis identified YAP1, ZEB1, H3-3B, and IGF1R as core hub genes, forming a central regulatory module involved in Hippo signaling, EMT, and PI3K-Akt pathways. Conclusion: This study clarified the expression and conservation characteristics of hsa_circ_0036683 in HCC and constructed a potential hsa_circ_0036683-miRNA-mRNA ceRNA regulatory network. The results provide novel bioinformatics insights for exploring the molecular mechanism of HCC, indicating that hsa_circ_0036683 has the potential to be a candidate biomarker and therapeutic target for HCC.
Downloads
References
[1] McGlynn, K. A., Petrick, J. L., & El Serag, H. B. (2021). Epidemiology of hepatocellular carcinoma. Hepatology, 73(Suppl. 1), 4–13. https://doi.org/10.1002/hep.31288.
[2] Gilles, H., Garbutt, T., & Landrum, J. (2022). Hepatocellular carcinoma. Critical Care Nursing Clinics of North America, 34(3), 289–301. https://doi.org/10.1016/j.cnc.2022.04.004.
[3] Kun, C., Ning, C., Jinghan, Z., et al. (2022). Tumor-associated macrophages in liver cancer: From mechanisms to therapy. Cancer Communications, https://doi.org/10.1002/cac2.12345.
[4] Greta, P., Claudia, S., Maristella, M., et al. (2024). Hepatocellular carcinoma old and emerging therapeutic targets. Cancers, 16(5), 901. https://doi.org/10.3390/cancers16050901.
[5] Zhao, X., Wang, Y., Xia, H., et al. (2023). Roles and molecular mechanisms of biomarkers in hepatocellular carcinoma with microvascular invasion: A review. Journal of Clinical and Translational Hepatology. https://doi.org/10.14218/ JCTH. 2022. 00013S.
[6] Wei-Yi, Z., Ze-Rong, C., Jia, L., et al. (2020). Circular RNA: metabolism, functions and interactions with proteins. Molecular Cancer.
[7] Liu, C. E. A. (2022). Circular RNAs: Characterization, cellular roles, and applications. Cell. https://doi.org/10.1016/j. cell. 2022. 04.021.
[8] Jundan, Z., Tianle, H., Jiaxin, C., et al. (2025). Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation. Journal of Advanced Research. https://doi. org/ 10. 1016/j.jare.2025.09.017.
[9] Chu-Xiao, L., & Ling-Ling, C. (2022). Circular RNAs: Characterization, cellular roles, and applications. Cell. https:// doi. org/10.1016/j.cell.2022.06.001.
[10] Margvelani, G., Maquera, K. A. A., Welden, J. R., et al. (2025). Translation of circular RNAs. Nucleic Acids Research, 53(1), gkae1167. https://doi.org/10.1093/nar/gkae1167.
[11] Li, F., Yang, Q., He, A. T., et al. (2021). Circular RNAs in cancer: Limitations in functional studies and diagnostic potential. Seminars in Cancer Biology, 75, 49–61. https:// doi. org/ 10.1016/j.semcancer.2020.10.002.
[12] Zheng, L., Fangming, Y., Zhun, X., et al. (2023). Review of novel functions and implications of circular RNAs in hepatocellular carcinoma. Frontiers in Oncology. https:// doi. org/ 10.3389/fonc.2023.1093063.
[13] Ziwei, T., Xue, L., Yanfeng, Z., et al. (2024). The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets. Frontiers in Cell and Developmental Biology. https://doi.org/ 10. 3389/fcell.2024.1341999.
[14] Xian, Z., Youxiu, Z., Xudong, W., et al. (2022). Advances in Circular RNA and Its Applications. International Journal of Medical Sciences. https://doi.org/10.7150/ijms.71840.
[15] Conn, V. M., Chinnaiyan, A. M., & Conn, S. J. (2024). Circular RNA in cancer. Nature Reviews Cancer, 24(9), 597–613. https://doi.org/10.1038/s41568-024-00721-7.
[16] Sunagawa, Y., Yamada, S., Sonohara, F., et al. (2021). Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue. Scientific Reports, 11(1), 6016. https://doi.org/ 10. 1038/ s41598-021-85237-y.
[17] Previn, G., & K. L. M. (2023). Hepatocellular carcinoma. Clinical Liver Disease. https://doi.org/ 10.1016/j.cld. 2022. 08. 004.
[18] Riccardo, N., Rachele, R., Livio, C., et al. (2023). Predictors of early and late hepatocellular carcinoma recurrence. World Journal of Gastroenterology, 29(8), 1243. https://doi.org/ 10. 3748/ wjg. v29. i8.1243.
[19] Federica, T., Chiara, G., Domenico, T., et al. (2024). Non-Coding RNAs as Potential Diagnostic Prognostic Markers for Hepatocellular Carcinoma. International Journal of Molecular Sciences, 25(22), 12235. https://doi.org/ 10.3390/ijms 252212 235.
[20] Gregor, J., & Tadeja, R. (2025). Circular RNA in hepatocellular carcinoma: emerging therapeutic strategies. Frontiers in Immunology. https://doi.org/10. 3389/fimmu. 2025. 1722576.
[21] Huang, X., Tang, F., Weng, Z., et al. (2019). MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway. Cancer Cell International, 19, 108. https://doi.org/10. 1186/ s12935-019-0818-x.
[22] Lou, C., Shi, J., & Xu, Q. (2022). Exosomal miR-626 promotes the malignant behavior of oral cancer cells by targeting NFIB. Molecular Biology Reports, 49(6), 4829–4840. https://doi.org/ 10.1007/s11033-022-07336-x.
[23] You, G., Cheng, A., Shen, E. Y., et al. (2023). MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2–GPX2 Molecular Axis in Head–Neck Cancer. Cells, 12(24), 2853. https://doi.org/10.3390/cells12242853.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
