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Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas

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Abstract

FSCN1 gene encodes an actin-bundling protein, FSCN1, which is involved in formation of actin-based structures that contribute to cell migration. High levels of FSCN1 expression is observed in cells with extended membranes and protrusions. Moreover, up-regulation of FSCN1 has been reported in several epithelial carcinomas. Therefore, FSCN1 is thought to play a role in cell movement and invasion. However, the mechanism behind FSCN1 up-regulation is not known. We investigated the expression of FSCN1 using immunohistochemistry. Methylation-specific PCR was adopted to analyze the methylation status of FSCN1 promoter as a potential regulatory mechanism in FSCN1 expression. The samples included papillary thyroid carcinoma, follicular thyroid carcinoma and goiter samples (controls). Methylation of FSCN1 promoter was observed in 50% of follicular, 48.6% of papillary and 60% of controls. The promoter was unmethylated in 16.7% of follicular samples, 5.7% of papillary samples and 26.7% of controls. In the remaining 33.3% of follicular and 45.7% of papillary samples as well as 13.3% of controls, both methylated and unmethylated alleles were amplified, a condition referred to as semi-methylation. The results showed that FSCN1 promoter was significantly hypomethylated in papillary cases while the methylation status was not significantly altered in follicular cases. On the other hand, FSCN1 was expressed in only nine papillary samples. Regarding protein expression and methylation status, we suggest that hypomethylation of FSCN1 promoter in papillary thyroid carcinoma does not lead to overexpression of FSCN1 and that there might be other regulatory mechanisms involved in FSCN1 up-regulation.

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Abbreviations

ATC:

Anaplastic thyroid carcinoma

BGS:

Bisulfite genomic sequencing

CBP:

CREB-binding protein

CREB:

cAMP responsive element

ESCC:

Esophageal squamous cell carcinoma

FFPE:

Formalin-fixed paraffin-embedded

FTC:

Follicular thyroid carcinoma

GSK-3β:

Glycogen synthase kinase

IHC:

Immunohistochemistry

kDa:

Kilodalton

MSP:

Methylation-specific PCR

MTC:

Medullary thyroid carcinoma

PTC:

Papillary thyroid carcinoma

siRNA:

Small-interfering RNA

TCF:

T cell factor/lymphocyte enhancer-binding factor 1

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Acknowledgements

We appreciate Mrs. Fereshteh Sarafrazi and Mrs. Roghaye Afkari of Specialized Medical Genetics Center (SMGC) of Academic Center for Education, Culture and Research (ACECR), Tehran University of Medical Sciences Branch for their assistance. We also thank the staff of pathology department at Dr. Shariati Hospital, Tehran University of Medical Sciences for providing us with samples and performing immunohistochemistry as well as Mr. Majid Mosahebi for providing us with bisulfate conversion kit. The authors would like to acknowledge Dr. Navid Kabuli and Dr. Hilda Samimi for their comments on the manuscript.

Funding

This study was funded by “Deputy of Research, Tehran University of Medical Sciences” and did not receive any funding from any other organizations including NIH, Welcome Trust, HHMI, etc.

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Poursina St, Tehran, Iran

    Mojdeh Mahdiannasser, Majid Kabuli & Mohsen Ghadami

  2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Poursina St, District 6, Tehran, Tehran Province, Iran

    Vahid Haghpanah, Bagher Larijani & Mohsen Ghadami

  3. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Vahid Haghpanah

  4. Specialized Medical Genetic Center (SMGC) of ACECR, 4th floor, No 65, Aboureihan St, Enghelab Ave., Tehran, Iran

    Elia Damavandi

  5. Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran

    Elia Damavandi

  6. Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Jalal Al Ahmad Junction, Karegar Shomali St, Tehran, Iran

    Seyed Mohammad Tavangar

  7. Cardiac Primary Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohsen Ghadami

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  1. Mojdeh Mahdiannasser
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Correspondence to Mohsen Ghadami.

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This study has been approved by the EMRI ethical committee. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Mahdiannasser, M., Haghpanah, V., Damavandi, E. et al. Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas. Mol Biol Rep 47, 2161–2169 (2020). https://doi.org/10.1007/s11033-020-05315-8

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