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Knockdown of SIX4 inhibits pancreatic cancer cells via apoptosis induction

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Abstract

Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the whole staff of the Immunology Research Center of Tabriz University of Medical Sciences and Gastroenterology and Liver Disease Research Center of Baqiyatallah University of Medical Sciences for their assistance in this research. We also thank the whole staff of the Imam Khomeini Hospital for providing cancer tissue samples.

Funding

This project was financially supported by the funds from the Tabriz University of Medical Sciences and Baqiyatallah University of Medical Sciences.

Author information

Authors and Affiliations

  1. Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Heiat & Mohammad Ali Abyazi

  2. Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Ehsan Rezaei

  3. Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Javad Gharechahi

  4. Department of Microbiology, Malekan Branch, Islamic Azad University, Malekan, Iran

    Masoumeh Abbasi

  5. Department of Genetics and Biotechnology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran

    Javad Behroozi

  6. Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran

    Javad Behroozi

  7. Immunology Research Center, Tabriz University of Medical Sciences, Gholghasht Ave, 5166614766, Tabriz, Iran

    Behzad Baradaran

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  1. Mohammad Heiat
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Contributions

BB, and MH conceived and designed research. ER and JG conducted the experiments. MA contributed new reagents or analytical tools. MA and JB analyzed the data. AI wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Behzad Baradaran.

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Conflict of interest

All authors declare that they have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication.

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This research was reviewed and approved by the Baqiyatallah University of Medical Sciences institutional review board. All participants were informed about the study and signed a consent form according to the Declaration of Helsinki ethical standards (the ethical code: IR.BMSU.REC.1399.426).

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Heiat, M., Rezaei, E., Gharechahi, J. et al. Knockdown of SIX4 inhibits pancreatic cancer cells via apoptosis induction. Med Oncol 40, 287 (2023). https://doi.org/10.1007/s12032-023-02163-x

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  • DOI: https://doi.org/10.1007/s12032-023-02163-x

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