Amelogenesis imperfecta is a congenital form of
enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these genes remains mostly unclear. To identify signatures of
biological pathways in
amelogenesis imperfecta, we conducted bioinformatic analyses on genes associated with the condition in humans. Through an extensive search of the main biomedical databases, we found 56 genes in which mutations and/or association/linkage were reported in individuals with
amelogenesis imperfecta. These candidate genes were further grouped by function, pathway,
protein-
protein interaction, and tissue-specific expression patterns using various bioinformatic tools. The bioinformatic analyses highlighted a group of genes essential for extracellular matrix formation. Furthermore, advanced bioinformatic analyses for
microRNAs (
miRNAs), which are short non-coding RNAs that suppress target genes at the post-transcriptional level, predicted 37 candidates that may be involved in
amelogenesis imperfecta. To validate the
miRNA-gene regulation association, we analyzed the target gene expression of the top seven candidate
miRNAs: miR-3195, miR-382-5p, miR-1306-5p, miR-4683, miR-6716-3p, miR-3914, and miR-3935. Among them, miR-1306-5p, miR-3195, and miR-3914 were confirmed to regulate ameloblast differentiation through the regulation of genes associated with
amelogenesis imperfecta in AM-1 cells, a human
ameloblastoma cell line. Taken together, our study suggests a potential role for
miRNAs in
amelogenesis imperfecta.