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Published on: January 22, 2018
Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU
Tahani Ahmad Almatrafi1, Natrayan Lakshmaiya2, Hailah M Almohaimeed3
1Anatomy Department, College of Medicine, King Saud University, Saudi Arabia.
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.
Insights
This study shows that miR-193a-5p, combined with 5-fluorouracil (5-FU), reduces matrix metalloproteinase 16 (MMP16) in gastric cancer. This combination effectively suppresses tumor growth and migration.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs and chemotherapy drugs are used to treat various cancers.
- Matrix metalloproteinase 16 (MMP16) and miR-193a-5p play roles in gastric cancer (GC) pathogenesis.
Purpose of the Study:
- Investigate the function of MMP16 and miR-193a-5p in gastric cancer.
- Evaluate the combined effect of miR-193a-5p and 5-fluorouracil (5-FU) on GC.
Main Methods:
- Assessed MMP16 and miR-193a-5p expression in GC tissues and cells using qPCR.
- Evaluated the impact of miR-193a-5p and 5-FU on MMP16 expression via qRT-PCR and Western blotting.
- Assessed cell viability, migration, and apoptosis using MTT, Scratch, and flow cytometry assays.
Main Results:
- MMP16 expression was elevated, while miR-193a-5p expression was decreased in GC.
- miR-193a-5p replacement down-regulated MMP16, especially with 5-FU co-administration.
- miR-193a-5p targeted MMP16, reducing GC cell migration and inducing apoptosis, enhanced by 5-FU.
Conclusions:
- miR-193a-5p and 5-FU combination therapy down-regulates MMP16 in gastric cancer.
- This therapeutic strategy suppresses tumor growth and migration in GC.
