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circRNA circ-MYBL2 is a novel tumor suppressor and potential biomarker in multiple myeloma

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Abstract

Currently, multiple myeloma (MM) is still an incurable disease. Deciphering its pathogenesis will bring new targets for clinical diagnosis and treatment. In the present study, we identified a MM-associated circular RNA (circRNA), circ-MYBL2, which was dramatically decreased in MM tissue and serum samples in comparison to normal samples. Low circ-MYBL2 level was closely correlated with high clinical stage and unfavorable outcome, and serum circ-MYBL2 had excellent accuracy in diagnosing MM. Exogenous circ-MYBL2 expression notably repressed MM cell viability, DNA synthesis and cell cycle progression. Further exploration revealed that circ-MYBL2 exerted the tumor-inhibiting effect by affecting the phosphorylation level of its linear isoform, in which circ-MYBL2 facilitated the binding of Cyclin F to MYBL2, dampening MYBL2 phosphorylation and activation, thereby inhibiting the transcription of a number of well-known proliferation-related oncogenes. Importantly, overexpression of circ-MYBL2 significantly reduced the tumor size of subcutaneous xenografts in nude mice. Taken together, our data unveil a regulatory mechanism linking circ-MYBL2 and its host gene mediated by Cyclin F, providing a potential diagnostic, prognostic and therapeutic target for MM patients.

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Funding

This study was supported by the Youth Talent Cultivation Project Fund of The First Affiliated Hospital of Jinzhou Medical University.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Jinzhou Medical University, No.2, Section 5, Renmin Street, Guta District, Jinzhou, 121000, Liaoning, China

    Shanshan Yu, Limei Ai, Wei Wei & Jing Pan

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  1. Shanshan Yu
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  2. Limei Ai
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  3. Wei Wei
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  4. Jing Pan
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Contributions

SSY, WW and JP performed the experiments, collected and analyzed the data. SSY drafted manuscript, and LMA provided the idea, edited and revised manuscript. All authors approved the final version.

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Correspondence to Limei Ai.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of The First Affiliated Hospital of Jinzhou Medical University, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All procedures performed in studies involving animals were in accordance with the Institutional Animal Care and Use Committee of The First Affiliated Hospital of Jinzhou Medical University.

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Yu, S., Ai, L., Wei, W. et al. circRNA circ-MYBL2 is a novel tumor suppressor and potential biomarker in multiple myeloma. Human Cell 34, 219–228 (2021). https://doi.org/10.1007/s13577-020-00441-8

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  • DOI: https://doi.org/10.1007/s13577-020-00441-8

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