Abstract
Background. Gastric cancer (GC) is a significant global health concern, ranking as the fifth most common malignant tumor and the fourth leading cause of cancer-related deaths worldwide. The primary treatment approach for metastatic GC is systemic chemotherapy. Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic enzymes that play crucial roles in various physiological processes. Among them, MMP9 is known for its complexity and its ability to degrade the components of the extracellular matrix. This study aimed to compare the expression of the MMP9 gene in cancerous and adjacent tissue of GC and evaluate its knockdown effects on GC cell line migration.
Methods. In the present study, 50 tumor tissues and adjacent non-tumor control tissues were collected from patients with GC. Using a real-time polymerase chain reaction, the expression levels of the MMP9 gene were assessed in these samples. Additionally, bioinformatics methods were employed to analyze MMP9 expression in a larger cohort of GC patients. Furthermore, a data mining study was conducted to investigate the potential impact of MMP9 expression on the overall survival of GC patients. In addition, appropriate small interfering RNA (siRNA) was synthesized to suppress the MMP9 oncogene and transfected into the GC cell line, and migration was investigated eventually.
Results. The results demonstrated significant upregulation of the MMP9 gene in tumor samples compared to tumor-adjacent samples, with a notable fold change of 4.6. This consistent finding was further supported by our bioinformatics analysis. Additionally, our pan-cancer analysis of TCGA data revealed that MMP9 is upregulated in various malignant tumors, indicating its potential relevance beyond GC. After MMP9 siRNA transfection, the migration rate of the cancer cells was evaluated by a wound-healing assay. The GC cell migration and invasion significantly decreased after the knockdown of MMP9 by specific siRNA.
Conclusion. In general, our study showed MMP9 upregulation in GC and suggested that the transfection of MMP9 gene siRNA could reduce invasion and migration.
Practical Implications. siRNAs are promising medical breakthroughs for the treatment of MMP9-related cancer invasion and migration. However, there is still a need to deepen our understanding of MMP9 gene function in tumorigenesis.