ELASTIN MICROFIBRIL INTERFACER 1 SUPPRESSES MELANOMA GROWTH THROUGH MT1-MMP INHIBITION: AN EXPERIMENTAL STUDY
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Date
2024-03-11
Authors
Shuqqo, Baraa
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Publisher
An-Najah National University
Abstract
Background: Melanoma is a type of skin cancer with a high mortality rate since it can spread to other organs in the body. The incidence rate has recently risen dramatically due to a variety of factors such as sun exposure. However, it is characterised by an imbalance between the oncogenes and tumour suppressor genes, which enhances the poor prognosis in melanoma patients. One of these overregulated genes is MT1-MMP while EMILIN-1 is considered a tumour suppressor gene that is proteolyzed and inactivated, enhancing melanoma's metastasis.
Aims: This study aims to determine the correlation between EMILIN-1 overexpression and the prognosis of melanoma through inhibition of MT1-MMP, also explores this relationship in light of potential therapeutic options.
Methods: Experimental study was performed An-Najah Laboratory for Cancer and Stem Cell Research, located in Nablus. B16F10 melanoma cells line model were seeded, and then lentivirus was used to overexpress the EMILIN-1 gene. To determine the impact of EMILIN-1 overexpression on tumor growth, the investigation was conducted in vivo using C57 BL6 mice and in vitro using the same cell lines. To highlight the fact that EMILIN-1 overexpression suppresses MT1-MMP expression, a q-PCR analysis of MT1-MMP and EMILIN-1 was performed.
Results: The results of the investigation indicated that EMILIN-1 was not highly expressed in the B16F10 cell line, whereas MT1-MMP was. This work shown that overexpressing EMILIN-1 can ameliorate the situation and decrease the growth of melanoma by blocking MT1-MMP, which may be used as a treatment for metastatic melanoma.
Conclusion: Despite tremendous efforts being made in this field, there has not yet been a viable treatment or a significant improvement in the survival rate of melanoma patients. The problem is exacerbated by the fact that patients have become resistant to chemotherapy drugs. One gene known to prevent tumor growth and spread is EMILIN-1. EMILIN-1 is downregulated in melanoma, which reduces its ability to control tumor growth and promotes the spread of cancer. MT1-MMP inhibition is the main focus of the study, along with the effects of overexpressing this gene to restore it. Due to its ability to suppress MT1-MMP, EMILIN-1 overexpression decreases the growth of melanoma in vitro and primary tumor cells in vivo.
Keywords: EMILIN-1, MT1-MMP, ERK1/2, METASTASIS, MELANOMA.