Identification of the combinatorial effect of miRNA family regulatory network in different growth patterns of gastric cancer and its clinical value

Abstract According to the growth pattern, gastric cancer (GC) could be classified into expanding-type GC and infiltrative-type GC (Ming’s classification). The growth pattern of GC is often related to the malignant degree, invasion, metastasis and other pathological characteristics of tumors. MicroRNAs (miRNAs) play important roles in modulating gene expression during the GC development. In this study, miR-29s were significantly correlated with the gastric carcinogenesis and Ming’s classification. Biological function of miR-29s is most closely related to the pathway of ECM-receptor interaction. ECM structural assembly, cell movement and cell adhesion are the main functional categories of target genes in this pathway. Among these targets, COL4A1 gene ranked the top in the association analysis combined miR-29s biological function and GC subtype, and miR-29s inhibited its translation by binding to the 3'-UTR region. Infiltrative-type GC cells secrete higher level of COL4A1 protein than expanding-type GC cells. The expression of COL4A1 in GC is correlated with clinicopathological features. Downregulation of COL4A1 expression significantly inhibited the migration and invasion of GC cells. High COL4A1 expression was correlated with poor prognosis in survival analysis. The miR-29s regulatory network may affect the development of growth patterns and pathological progress of GC by regulating the function of COL4A1.