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Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin)

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Abstract

Background

Anticancer genes are an endogenous defense against transformed cells as they impose antineoplastic effects upon ectopic expression. Profiling the expression of these genes is fundamental for exploring their prognostic and therapeutic relevance in cancers. Natural compounds can upregulate anticancer genes in malignant cells and thus be useful for therapeutic purposes. In this study, we identified the expression levels of anticancer genes in breast cancer clinical isolates. In addition, the purified and sequenced plant protein (riproximin) was evaluated for its potential to induce anticancer genes in two breast cancer cell lines.

Methodology

Expression profiles of three anticancer genes (NOXA, PAR-4, TRAIL) were identified by immunohistochemistry in 45 breast cancer clinical isolates. Breast cancer cells were exposed to riproximin and expression of the anticancer genes was determined by microarray, real-time PCR and western blot methodologies. Lastly, a bioinformatic approach was adopted to highlight the molecular/functional significance of the anticancer genes.

Results

NOXA expression was evenly de-regulated among the clinical isolates, while PAR-4 was significantly down-regulated in majority of the breast cancer tissues. In contrast, TRAIL expression was increased in most of the clinical samples. Expression levels of the anticancer genes followed a distinct trend in accordance with the disease severity. Riproximin showed a substantial potential of inducing expression of the anticancer genes in breast cancer cells at transcriptomic and protein levels. The bioinformatic approach revealed involvement of anticancer genes in multiple cellular functions and signaling cascades.

Conclusion

Anticancer genes were de-regulated and showed discrete expression patterns in breast cancer patient samples. Riproximin effectively induced the expression of selected anticancer genes in breast cancer cells.

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Data availability

The datasets generated during the current study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan

    Asim Pervaiz, Talha Saleem, Syed Mohsin Raza, Iqra Shaukat, Kinzah Kanwal & Osheen Sajjad

  2. Toxicology and Chemotherapy Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany

    Asim Pervaiz & Martin R. Berger

  3. Morbid Anatomy and Histopathology Department, University of Health Sciences, Lahore, Pakistan

    Nadia Naseem

  4. Department of Allied Health Sciences, Superior University, Lahore, Pakistan

    Talha Saleem

  5. Human Genetics and Molecular Biology Department, University of Health Sciences, Lahore, Pakistan

    Sana Iqbal

  6. Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

    Faiza Shams & Bushra Ijaz

  7. Immundiagnostik Comp, Bensheim, Germany

    Martin R. Berger

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  1. Asim Pervaiz
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  2. Nadia Naseem
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Contributions

AP conceived this study, supervised/analysed the experiments and wrote the manuscript draft. NN supervised clinical sampling/immunohistochemistry and drafted the relevant findings. TS, IS, KK and OS helped in transcriptomic expression profiling and preparation of figures. SMR performed the bioinformatic analysis of this study. SI, FS and BI provided the support in western blot analysis. MRB facilitated the microarray experiments and also supervised the drafting/editing of the manuscript.

Corresponding author

Correspondence to Asim Pervaiz.

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For clinical investigations, informed consent was obtained from all patients and the study was conducted in accordance with the guidelines of the Ethics Review Committee of the University of Health Sciences, Lahore, Pakistan. Furthermore, the procedures performed were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendmentsor comparable ethical standards.

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Pervaiz, A., Naseem, N., Saleem, T. et al. Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin). Mol Biol Rep 50, 5209–5221 (2023). https://doi.org/10.1007/s11033-023-08477-3

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