FEATURES OF COLLAGENASE GENE EXPRESSION IN BREAST CANCER TISSUE:AN OPEN DATABASES ANALYSIS

Abstract

Summary. Breast cancer (BCa) is the most common cancer among women both in Ukraine and in the world. Extracellular matrix remodeling has been shown to play a crucial role in tumor progression. Collagenases are one of the main drivers of this process, providing collagen degradation and directly affecting the invasion and metastasis of neoplastic cells. Aim: to study the features of collagenase gene expression and their regulatory factors in BC tissue as possible drivers of tumor growth. Objects and methods: a comparison of collagenase gene expression levels in normal and malignant breast tissue was performed using the GEPIA, UALCAN, and TNMplot resources. The methylation levels of collagenase gene promoters were determined using the UALCAN database. The identification of microRNAs and transcription factors involved in the regulation of collagenase expression was performed based on the information provided on the miRNet v2.0 platform using the TarBase v.8.0 and JASPAR databases. The miRNA level study was performed using the miR-TV online resource. Results: it was found that BCa tissue is characterized by significantly higher MMP1, MMP8, and MMP13 mRNA expression levels compared to normal breast tissue. It was demonstrated that the methylation levels of MMP1 and MMP13 promoters in tumor cells were significantly lower compared to non-transformed breast cells. Using the TarBase v.8.0 and JASPAR databases, transcription factors and miRNAs involved in the regulation of MMP1, MMP8, and MMP13 expression were identified. Analysis of the expression levels of miRNAs involved in the regulation of collagenase expression showed that the levels of miR-155-5p, miR-200b-3p, and miR-210-5p in BCa tissue were 2.26 (p = 2.2e-16), 2.95 (p = 2.2e-16), and 5.90 (p = 2.2e-16) times higher, respectively, compared to non-transformed breast tissue. It was shown that BC tissues compared to healthy donor tissues were characterized by significantly lower expression levels of miR-100-5p, miR-127-3p, and miR-539-5p by 4.19 (p = 2.2e-16), 2.05 (p = 3.9e-12), and 1.70 (p = 2.5e-5), respectively. Conclusions: the obtained results indicate the involvement of collagenases in the development and progression of malignant tumors and indicate the need for further research on their role in the formation of the aggressive potential of BC.