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The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells

Abstract

The era of induced pluripotent stem cells (iPSCs) was used as novel biotechnology to replace embryonic stem cells bypassing the ethical concerns and problems of stem cell transplant rejection. The anti-tumour potential of iPSCs against many tumours including salivary cancer was proven in previous studies. The current study aimed to investigate the contribution of the Bax, Sirt-1, TGF-β, and MALAT genes and/or their protein expression to the pathogenesis of submandibular carcinogenesis before and after iPSCs treatment. Thirty Wistar albino rats were equally assigned into three groups: group I (control), group II (Squamous cell carcinoma (SCC)): submandibular glands were injected SCC cells, and group III (SCC/iPSCs): SCC rats were treated by 5 × 106 iPSCs. Submandibular gland sections were subjected to histological and immunohistochemical analyses to detect mucopolysaccharides, Bax, and TGF-β expression as well as PCR quantification for TGF-β, Sirt-1, and lncRNA MALAT-1 gene expressions. Western blotting was also used to detect Sirt-1 and TGF-β protein expressions. SCC group revealed infiltration by sheets of malignant squamous cells with or without keratin pearls and inflammatory cells, in addition to upregulation of TGF-β, Sirt-1, MALAT-1, and Bax, whereas SCC/iPSCs group showed an improved submandibular histoarchitecture with the maintenance of the secretory function. Bax and TGF-β immunoexpression were significantly reduced. The upregulated TGF-β, Sirt-1, and MALAT-1 genes were significantly decreased. iPSCs protected against the experimentally induced submandibular gland carcinoma that might be achieved via their regenerative potential and their regulatory modulation of Sirt-1, TGF-β, and MALAT-1 gene/protein expressions and of the apoptotic response in cancer cells.

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Data availability

All data generated or analysed in the current study were included in the published article and any further data are on reasonable request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors

Contributions

EF: Writing the paper, searching the data, and doing the histological sections. YAE: Collecting literature search. AM interpreted and wrote the figure legends, wrote initial draft, and participated in discussion. DS: preparing the cells and doing the biochemical analysis. NT analysed and correlated the results. EM: doing the gene analysis and participating in writing the manuscript.

Corresponding author

Correspondence to Ahmed A. Morsi.

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All authors have no conflict of interest to declare.

Ethical approval

The animals were brought from the animal house for laboratory experimentation and animal surgery at the Faculty of Medicine, Cairo University, Cairo, Egypt. Animal care and husbandry and all experimental-related ethical issues were legalized by the Ethical Committee for Scientific Research at the Faculty of Medicine, Cairo University, Egypt (Approval #: IORG00010305).

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Cite this article

Faruk, E.M., Sabry, D., Morsi, A.A. et al. The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-021-04255-6

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Keywords

  • Immunohistochemistry
  • Induced pluripotent stem cells
  • lncRNA
  • MALAT-1
  • Submandibular salivary cancer
  • Sirt-1
  • TGF-β gene expressions