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Overexpression of miRNA-9 enhances galectin-3 levels in oral cavity cancers

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Abstract

Oral cavity cancer (OCC) is the predominant subtype of head and neck cancer (HNC) and has up to 50% mortality. Genome-wide microRNA (miR) sequencing data indicates overexpression of miR-9-5p in HNC tumours, however, the biological role of miR-9-5p in OCC is complex; it can either act as a tumour suppressor or an oncomir, regulating many target genes at the post-transcriptional level. We have investigated the overexpression of miR-9-5p in three OCC cell lines. We have evaluated its expression levels and Galectin-3 as potential biomarkers in saliva samples collected from controls and OCC patients. We found that over expression of miR-9-5p in OCC cell lines resulted in a significant reduction in cell proliferation and migration, and an increase in apoptosis, which was paralleled by an increase in Galectin-3 secretion and export of Galectin-3 protein. Our data are consistent with miR-9-5p being a modulator of Galectin-3 via the AKT/γ-catenin pathway. In addition, the positive correlation between the levels of miR-9-5p expression and secreted Galectin-3 in saliva reflects a similar relationship in vivo, and supports the utility of their integrative evaluation in OCC. Our findings indicate that both miR-9-5p and Galectin-3 are critical biomolecules in the progression of OCC.

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All data generated or analysed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

We would like to thank the members of Saliva & Liquid Biopsy Translational Laboratory for their assistance in sample collection and processing. We also thank Trang Le, Jennifer Edmunds, Charmaine Micklewright, Jacqui Keller and Dana Middleton and the staff at the Royal Brisbane Women’s Hospital (RBWH) and the Princess Alexandra Hospital (PAH) for their assistance in head and neck cancer patients recruitment.

Funding

CP is funded by the Cancer Australia Grant (APP1145657), NHMRC Ideas Grant (APP 2002576) and the National Institutes of Health Grant (1R21EB030349-01).

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Authors and Affiliations

  1. Saliva & Liquid Biopsy Translational Laboratory, Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Room 603D, 60 Musk Avenue, Brisbane, QLD, 4059, Australia

    Yunxia Wan, Xi Zhang, Kai Dun Tang, Tony Blick, Erik W. Thompson & Chamindie Punyadeera

  2. Translational Research Institute, Brisbane, QLD, Australia

    Yunxia Wan, Xi Zhang, Kai Dun Tang, Tony Blick, Erik W. Thompson & Chamindie Punyadeera

  3. School of Medicine, University of Queensland, Brisbane, QLD, 4029, Australia

    Liz Kenny

  4. Queensland Health, Royal Brisbane and Women’s Hospital, Brisbane, QLD, 4029, Australia

    Liz Kenny

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  1. Yunxia Wan
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Contributions

All authors have read and agreed to the published version of the manuscript. Conceptualization—CP, methodology, YXW, formal analysis, data curation and investigation, all authors; writing—original draft preparation, YXW and KDT; writing—review and editing, all authors; funding acquisition, CP.

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Correspondence to Chamindie Punyadeera.

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The authors declare no conflict of interest.

Ethical approval

This study was approved by the University of Queensland (UQ) Medical Ethical Institutional Board (HREC No: 2014000679 and 2014000862), the Princess Alexandra Hospital (PAH) Ethics Review Board (HREC/12/QPAH/381) and Queensland University of Technology (QUT) (HREC No: 1400000617 and 1400000641).

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All the participants provided written informed consent prior to recruitment and sample collection and could withdraw at any time. The study was performed in accordance with the Declaration of Helsinki.

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Wan, Y., Zhang, X., Tang, K.D. et al. Overexpression of miRNA-9 enhances galectin-3 levels in oral cavity cancers. Mol Biol Rep 48, 3979–3989 (2021). https://doi.org/10.1007/s11033-021-06398-7

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