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Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells

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Abstract

Cancer, the leading cause of death worldwide, has witnessed significant advancements in treatment through targeted therapies. Among the proto-oncogenes prevalent in human cancers, KRAS stands out, and recent research has focused on long noncoding RNAs (lncRNAs) as regulators of miRNAs targeting the KRAS oncogene. This study specifically explores lncRNAs involved in the KRAS pathway in colorectal cancer (CRC). To investigate this, researchers employed iron oxide nanoparticles coated with glucose and conjugated with Oleuropein (Fe3O4@Glu-Oleuropein NPs) to evaluate their impact on candidate lncRNAs associated with KRAS pathway deregulation. The study utilized TCGA data to identify genes affected by KRAS mutation and lncRNAs linked to KRAS in CRC. Enrichr and MsigDB databases helped identify relevant pathways. Genes with a correlation coefficient above 0.5 and a P-value less than 0.01 with candidate lncRNAs were selected. MTT and flow cytometry assays determined the anti-proliferative and apoptotic effects of Fe3O4@Glu-Oleuropein NPs on CRC cells (SW480) and normal cells (HEK293). The findings showed that increased expression of FEZF1-AS1, GAS6-AS1, and LINC00920 correlated with mutated KRAS, and co-expressed genes were significantly involved in hypoxia, KRAS signaling, DNA repair, and IL-2/STAT5 signaling pathways. Fe3O4@Glu-Oleuropein NPs exhibited higher toxicity toward cancer cells, with IC50 values of 92 μg/ml for SW480 and 281 μg/ml for HEK293. Flow cytometry analysis revealed a substantial increase in necrotic and apoptotic cells when treated with Fe3O4@Glu-Oleuropein, along with down-regulation of GAS6-AS1, LINC00920, and FEZF1-AS1 lncRNAs in treated cells. In conclusion, this study highlights the therapeutic potential of Fe3O4@Glu-Oleuropein on colon cancer cells in vitro. The identification of lncRNAs involved in the KRAS pathway provides insights into the underlying mechanisms and offers avenues for further research in targeted cancer therapies.

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Data Availability

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

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Acknowledgements

The authors would like to thank to Mr. Mohamad Mahdevar for his help in bioinformatics section.

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Authors and Affiliations

  1. Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran

    Zahra Mahdavi Niyaki & Ali Salehzadeh

  2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Maryam Peymani

  3. Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran

    Mohammad Zaefizadeh

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Contributions

A.S., M. Z. and M.P. :Conceptualization. A.S., M. Z. and M.P.:Methodology. A.S. and M.P. :Formal analysis and investigation. A.S., Z. M.N. and M.P.: Writing Original Draft Preparation. Z. M.N. :Resources. A.S., M. Z. and M.P.:Supervision

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Correspondence to Ali Salehzadeh or Maryam Peymani.

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Mahdavi Niyaki, Z., Salehzadeh, A., Peymani, M. et al. Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells. Biol Trace Elem Res 202, 3073–3085 (2024). https://doi.org/10.1007/s12011-023-03892-w

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