Abstract
Background & Aims
Medulloblastoma (MB) is a primary malignant tumor of the brain. They are categorized as WHO grade IV neoplasms, and mostly occur in children. The traditional therapy for MB is surgery, followed by radiation and chemotherapy, but the clinical outcome is still poor and has a high possibility of recurrence. The mechanism underlying the development of MB should be further investigated to develop novel therapeutic strategies.
Methods
Research has demonstrated that circRNAs contribute to tumorigenesis, but the functional mechanism of circRNAs in MB has not been fully explored and remains vague. The differentially expressed circRNAs between MB and normal cerebellar tissues were analyzed based on the microarray expression profiles to characterize the potential mechanism of circRNAs in MB.
Results
The results revealed that circRNA_103128 was highly expressed in MB, and cellular and animal experiments were performed to verify its tumorigenic effect in MB. Furthermore, a bioinformatics analysis and literature review previous literature were performed, confirming miR-129-5p as a target gene downstream of circRNA_103128. In addition, SOX4 was predicted to be a downstream target protein of miR-129-5p. Subsequently, miR-129-5p expression was inhibited, which revealed the regulatory mechanism of circRNA_103128. The latter promotes MB cell growth, migration, and invasion by the sponge effect of miR-129-5p, thereby affecting the expression of SOX4.
Conclusions
This study is the first to systematically demonstrate that circRNA_103128 may play an important regulatory role in MB through a sponge effect with miR-129 -5p, which affects SOX4 expression and regulates tumorigenesis and tumor cell development in MB.
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Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank all members of the Key Laboratory of Neurology of Gansu Province, the Department of Neurosurgery of Lanzhou University Second Hospital.
Funding
Funding was supported by Natural Science Foundation of Gansu Province (18JR3RA365, 2021RCXM096, 21JR7RA420, 21JR7RA426, 20JR10RA758), Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (CY2022-QN-B05), National Natural Science Foundation of China (81960541, 82060455), Lanzhou Science and Technology Bureau (2018-1-109).
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YP and GY conceived the study and carried out its design. HY, YZ, XH, and QL performed the experiments. QD, YL, XW conducted the statistical analyses. HY wrote the paper; GY and YP revised the paper. All authors read and approved the final manuscript.
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Hang Yin, Yingnan Zhao and Yang Liu contributed equally to this work.
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Yin, H., Zhao, Y., Han, X. et al. Circ_103128 is associated with the tumorigenesis of medulloblastoma. J Cancer Res Clin Oncol 149, 11339–11349 (2023). https://doi.org/10.1007/s00432-023-04999-2
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DOI: https://doi.org/10.1007/s00432-023-04999-2