Sains Malaysiana 53(6)(2024): 1243-1253

http://doi.org/10.17576/jsm-2024-5306-02

Matrix Metallopeptidase 3 Coding SNPs Suppress Cell Invasion in MCF7 Breast Cancer Cells

(Pengekodan Matriks Metallopeptidase 3 SNPs Menekan Pencerobohan Sel dalam Sel Kanser Payudara MCF7)

SHAFINAH AHMAD SUHAIMI^1,4, SOON CHOY CHAN², PEI PEI CHONG³, NORAZALINA SAAD⁴*, DE MING CHAU⁵ & ROZITA ROSLI^4,

¹Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200, Kepala Batas, Pulau Pinang, Malaysia

²School of Liberal Arts, Science and Technology, Perdana University, 50490 Kuala Lumpur, Malaysia

³School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, 47500 Subang Jaya, Selangor, Malaysia

⁴UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁵Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Diserahkan: 17 April 2023/Diterima: 1 Februari 2024

Abstract

Matrix metallopeptidase 3 (MMP3) is among the key players in breast cancer metastasis that contributes to the highest cancer-related deaths in females globally. Previously, in silico analyses had shown that several coding single nucleotide polymorphisms (SNPs) of MMP3 were predicted to alter the secondary structures of MMP3 and subsequently reduce its mRNA stability. To validate the mentioned hypotheses, this study aimed to determine the effects of six coding SNPs of MMP3 on its mRNA stability, protein expression level as well as cell invasiveness in vitro. In this study, breast adenocarcinoma MCF7 cells were transfected with MMP3 wild type (MMP3-WT) and a variant containing SNPs (MMP3-Var). Following transfection, protein expression level, mRNA stability and enzyme activity of MMP3-WT and MMP3-Var were evaluated. Finally, the effect of MMP3 coding SNPs on cell invasiveness in breast cancer was determined. In this study, the mRNA stability, protein expression level and enzymatic activity of MMP3-Var were significantly reduced. Moreover, the presence of MMP3 coding SNPs led to attenuated invasiveness of transfected MCF7 cells. In conclusion, these findings may contribute to the current understanding of these coding SNPs with metastasis in breast cancer.

Keywords: Carcinoma; in vitro; MMP3; mammary; metastasis; stromelysin-1

Abstrak

Matriks metallopeptidase 3 (MMP3) adalah salah satu daripada pemain utama bagi metastasis kanser payudara yang menyumbang kepada kematian berkaitan kanser yang tertinggi dalam kalangan wanita di seluruh dunia. Sebelum ini, analisis in silico menunjukkan bahawa beberapa polymorfisme nukleotida tunggal (SNPs) pengekodan MMP3 diramalkan untuk mengubah struktur sekunder MMP3 dan seterusnya mengurangkan kestabilan mRNA. Bagi mengesahkan hipotesis tersebut, kajian ini bertujuan untuk mengenal pasti kesan in vitro enam SNPs pengekodan MMP3 ke atas kestabilan mRNA, tahap pengekspresan protein dan kemansangan sel. Dalam kajian ini, sel karsinoma payudara MCF7 telah ditransfeksi dengan MMP3 jenis liar (MMP3-WT) dan varian mengandungi SNPs (MMP3-Var). Selepas transfeksi, tahap pengekspresan protein, kestabilan mRNA serta aktiviti enzim bagi MMP3-WT dan MMP3-Var telah dinilai. Akhirnya, kesan SNPs pengekodan MMP3 terhadap kemansangan sel kanser payudara telah ditentukan. Kestabilan mRNA, tahap pengekspresan protein dan aktiviti enzim MMP3-Var menurun dengan signifikan. Tambahan pula, SNPs pengekodan MMP3 merencat kemansangan sel-sel MCF7 yang telah ditransfeksi. Kesimpulannya, hasil kajian ini boleh menyumbang kepada pemahaman semasa mengenai SNP pengekodan ini dengan metastasis dalam kanser payudara.

Kata kunci: Karsinoma; in vitro; mamari; MMP3; metastasis; stromelysin-1

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*Pengarang untuk surat-menyurat; email: norazalina@upm.edu.my