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High-throughput RNA sequencing identifies the miRNA expression profile, target genes, and molecular pathways contributing to growth of sporadic vestibular schwannomas

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Abstract

Purpose

To assess the differences in the miRNA expression profile between small (stage I Koos classification) and large solid vestibular schwannoma (VS) tumors, using the RNA-seq technique.

Methods

Twenty tumor samples (10 small and 10 large tumors) were collected from patients operated for VS in a Tertiary Academic Center. Tumor miRNA expression was analyzed using high-throughput RNA sequencing (RNA-seq) technique, with NovaSeq 6000 Illumina system. Bioinformatics analysis was done using statistical software R. Gene enrichment and functional analysis was performed using miRTargetLink 2.0 and DIANA miRpath 3.0 online tools.

Results

We identified 9 differentially expressed miRNAs in large VS samples: miR-7, miR-142 (-3p and -5p), miR-155, miR-342, miR-1269, miR-4664, and miR-6503 were upregulated, whereas miR-204 was significantly down-regulated in comparison to small VS samples. Gene enrichment analysis showed that the most enriched target genes were SCD, TMEM43, LMNB2, JARID2, and CCND1. The most enriched functional pathways were associated with lipid metabolism, along with signaling pathways such as Hippo and FOXO signaling pathway.

Conclusion

We identified a set of 9 miRNAs that are significantly deregulated in large VS in comparison to small, intracanalicular tumors. The functional enrichment analysis of these miRNAs suggests novel mechanisms, such as that lipid metabolism, as well as Hippo and FOxO signaling pathways that may play an important role in VS growth regulation.

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Data availability

The datasets generated and analyzed during the current study are available from the public repository Figshare under the link: https://figshare.com/account/articles/24466999. Additional data is available from corresponding author on reasonable request.

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Funding

This work was financially supported by the Medical University of Warsaw (research grant no. 1WF/1/M/MBS/N/21) and National Science Centre in Poland (research grant no. 2021/05/X/NZ5/00199).

Warszawski Uniwersytet Medyczny,1WF/1/M/MBS/N/21,Małgorzata Litwiniuk-Kosmala,Narodowe Centrum Nauki,2021/05/X/NZ5/00199,Małgorzata Litwiniuk-Kosmala

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Warsaw Medical University, Warsaw, Poland

    Małgorzata Litwiniuk-Kosmala, Maria Makuszewska, Kazimierz Niemczyk & Robert Bartoszewicz

  2. Laboratory of Sequencing, Nencki Institute of Experimental Biology, Warsaw, Poland

    Bartosz Wojtas & Bartłomiej Gielniewski

Authors
  1. Małgorzata Litwiniuk-Kosmala
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  2. Maria Makuszewska
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  3. Kazimierz Niemczyk
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  5. Bartosz Wojtas
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  6. Bartłomiej Gielniewski
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Contributions

All authors contributed to the study conception and design. Patient selection and sample collection were performed by Małgorzata Litwiniuk-Kosmala, Maria Makuszewska, Kazimierz Niemczyk, and Robert Bartoszewicz. Material preparation and laboratory analyses were performed by Bartłomiej Gielniewski. Data collection and analysis were performed by Bartosz Wojtas and Małgorzata Litwiniuk-Kosmala. The first draft of the manuscript was written by Małgorzata Litwiniuk-Kosmala, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Małgorzata Litwiniuk-Kosmala.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Medical University of Warsaw (approval no. KB/146/2021).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Litwiniuk-Kosmala, M., Makuszewska, M., Niemczyk, K. et al. High-throughput RNA sequencing identifies the miRNA expression profile, target genes, and molecular pathways contributing to growth of sporadic vestibular schwannomas. Acta Neurochir 166, 71 (2024). https://doi.org/10.1007/s00701-024-05984-5

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