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Role of Nischarin in the pathology of diseases: a special emphasis on breast cancer

Oncogene volume 41, pages 1079–1086 (2022)Cite this article

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Abstract

Nischarin has been demonstrated to have tumor suppressor functions. In this review, we comprehensively discuss up to date information about Nischarin. In addition, this paper aims to report the prognostic value, clinical relevance, and biological significance of the Nischarin gene (NISCH) in breast cancer (BCa) patients using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) datasets. We evaluated NISCH gene expression and its correlation to patient survival, baseline expression, and expression variation based on age groups, tumor stage, tumor size, tumor grade, and lymph node status in different subtypes of BCa. Since NISCH has been extensively reported to inhibit EMT and cancer cell migration, we also checked for the correlation between NISCH and EMT genes in addition to the correlation between NISCH and cell migration genes. Our results indicate that NISCH is a tumor suppressor that plays a critical role in BCa initiation, progression, and tumor development. We find that there is a higher level of NISCH expression in normal breast tissues compared to breast cancer tissues. Also, aggressive subtypes of breast cancers, such as the triple negative/basal category, have decreased levels of NISCH as the disease progresses. Finally, we report that NISCH is inversely correlated with many EMT and cancer cell migration genes in BCa. Interestingly, we identified a significant negative correlation between NISCH expression and its methylation in breast cancer patients. Overall, the goal of this report is to establish a strong clinical basis for further investigation into the cellular, molecular, and physiological roles of NISCH in BCa. Ultimately, NISCH gene expression might be clinically harnessed as a biomarker or predictor of invasiveness and metastasis in BCa.

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Fig. 1: Signaling pathways regulated by Nischarin.
Fig. 2: Mutation diagram for NISCH gene (exons) and protein from The Cancer Genome Atlas (TCGA) extracted from cBioPortal (https://www.cbioportal.org).
Fig. 3: Nischarin expression is associated with tumor subtype, grade, stage, size and DNA methylation status in breast cancer patients.
Fig. 4: Correlation analysis between NISCH and other genes.

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Acknowledgements

We wish to thank the Fred G. Brazda Foundation and the Department of Biochemistry and Molecular Biology, Louisiana State University School of Medicine and Health Sciences Center, New Orleans, for their financial support.

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  1. These authors contributed equally: Samuel C. Okpechi, Hassan Yousefi.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Louisiana State University School of Medicine and Health Sciences Center, New Orleans, LA, USA

    Samuel C. Okpechi, Hassan Yousefi & Suresh K. Alahari

  2. Stanley S. Scott Cancer Center, Louisiana State University School of Medicine and Health Sciences Center, New Orleans, LA, USA

    Samuel C. Okpechi, Hassan Yousefi & Suresh K. Alahari

  3. Section of Hematology & Medical Oncology, Tulane University School of Medicine, New Orleans, LA, USA

    Khoa Nguyen, Thomas Cheng, Bridgette Collins-Burow & Matthew E. Burow

  4. Louisiana State University Biological Sciences, Baton Rouge, LA, USA

    Nikhilesh V. Alahari

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Contributions

SO wrote the first draft, HY did bioinformatic analysis and prepared figures, KN, NA, BB, MB contributed to the text, TC created some figures, and SKA finalized the text and figures.

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Correspondence to Suresh K. Alahari.

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Okpechi, S.C., Yousefi, H., Nguyen, K. et al. Role of Nischarin in the pathology of diseases: a special emphasis on breast cancer. Oncogene 41, 1079–1086 (2022). https://doi.org/10.1038/s41388-021-02150-4

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