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

Adv Med Sci. 2024 Sep;69(2):463-473. doi: 10.1016/j.advms.2024.09.008. Epub 2024 Sep 26.

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.

Keywords: 5-Fluorouracil; Gastric cancer; MMP16; Metastasis; miR-193a-5p.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Fluorouracil* / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 16* / genetics
  • Matrix Metalloproteinase 16* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • MicroRNAs
  • Fluorouracil
  • MIRN193 microRNA, human
  • Matrix Metalloproteinase 16
  • MMP16 protein, human
  • Antimetabolites, Antineoplastic