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Войти в исследования Advances in medical sciences · 2024
Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU.
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Almatrafi Tahani Ahmad, Lakshmaiya Natrayan, Almohaimeed Hailah M, Chakravarthi Srikumar, Amin Ali H, Jafer Ayman, Almars Amany I, Basabrain Ammar A, Alghamdi Youssef S, Saadh Mohamed J, Akhavan-Sigari Reza
Аннотация
PURPOSE: Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC).
MATERIALS/METHODS: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients.
RESULTS: The current study found that while MMP16 expression increased in GC patients (P < 0.0001), miR-193a-5p expression significantly decreased (P < 0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P < 0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p.
CONCLUSIONS: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.
MATERIALS/METHODS: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients.
RESULTS: The current study found that while MMP16 expression increased in GC patients (P < 0.0001), miR-193a-5p expression significantly decreased (P < 0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P < 0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p.
CONCLUSIONS: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.