Tahani Ahmad Almatrafi , Natrayan Lakshmaiya , Hailah M. Almohaimeed , Srikumar Chakravarthi , Ali H. Amin , Ayman Jafer , Amany I. Almars , Ammar A. Basabrain , Youssef S. Alghamdi , Mohamed J. Saadh , Reza Akhavan-Sigari
{"title":"Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU","authors":"Tahani Ahmad Almatrafi , Natrayan Lakshmaiya , Hailah M. Almohaimeed , Srikumar Chakravarthi , Ali H. Amin , Ayman Jafer , Amany I. Almars , Ammar A. Basabrain , Youssef S. Alghamdi , Mohamed J. Saadh , Reza Akhavan-Sigari","doi":"10.1016/j.advms.2024.09.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>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).</div></div><div><h3>Materials/methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 463-473"},"PeriodicalIF":2.5000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in medical sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1896112624000567","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Advances in Medical Sciences is an international, peer-reviewed journal that welcomes original research articles and reviews on current advances in life sciences, preclinical and clinical medicine, and related disciplines.
The Journal’s primary aim is to make every effort to contribute to progress in medical sciences. The strive is to bridge laboratory and clinical settings with cutting edge research findings and new developments.
Advances in Medical Sciences publishes articles which bring novel insights into diagnostic and molecular imaging, offering essential prior knowledge for diagnosis and treatment indispensable in all areas of medical sciences. It also publishes articles on pathological sciences giving foundation knowledge on the overall study of human diseases. Through its publications Advances in Medical Sciences also stresses the importance of pharmaceutical sciences as a rapidly and ever expanding area of research on drug design, development, action and evaluation contributing significantly to a variety of scientific disciplines.
The journal welcomes submissions from the following disciplines:
General and internal medicine,
Cancer research,
Genetics,
Endocrinology,
Gastroenterology,
Cardiology and Cardiovascular Medicine,
Immunology and Allergy,
Pathology and Forensic Medicine,
Cell and molecular Biology,
Haematology,
Biochemistry,
Clinical and Experimental Pathology.