利用 miR-193a-5p 和 5-FU 靶向 MMP16 降低胃癌细胞株的转移能力

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences Pub Date : 2024-09-01 DOI:10.1016/j.advms.2024.09.008

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

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引用次数: 0

摘要

目的：microRNAs与化疗药物联合应用可有效治疗多种癌症。本研究试图探讨基质金属蛋白酶16（MMP16）和miR-193a-5p在胃癌（GC）发病机制中的功能：65例手术患者（其中15例接受了5-氟尿嘧啶（5-FU）治疗）提供了GC和邻近的非癌组织。然后，使用 qPCR 评估 GC 细胞中 MMP16 和 miR-193a-5p 的表达水平。使用 qRT-PCR 和 Western 印迹法评估了 miR-193a-5p 和 5-FU 给药对 MMP16 mRNA 表达的影响。还进行了 MTT 和划痕试验，以评估它们对细胞活力和迁移的影响。此外，还利用 MTT 试验进行了挽救实验。使用流式细胞术计算了细胞凋亡率。最后，还评估了 MMP16 和 miR-193a-5p 与患者临床病理特征的关系：结果：目前的研究发现，虽然 MMP16 在 GC 患者（PConclusions.）中的表达增加，但 miR-193a-5p 在 GC 患者中的表达却没有增加：这些研究结果表明，miR-193a-5p 与 5-FU 联用可下调 MMP16 在 GC 中的表达，从而抑制肿瘤生长。

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Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU

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.

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来源期刊

Advances in medical sciences 医学-医学：研究与实验

CiteScore

5.00

自引率

0.00%

发文量

审稿时长

25 days

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.