Fig 2: miR-137 is predicted to regulate the progression of CC via TGF-ß1/smad pathway by binding to GREM1. a The heat map of the top 50 genes with the highest differential expression where the X-axis represents the sample number, the Y-axis represents genes. The left dendrogram indicates gene expression cluster in which each small square in the graph represents the expression of a gene in one sample, and the histogram of the upper right is the color gradation in which blue stands for low expression and red stands for high expression; b GO analysis of DEGs of GSE63514; the X-axis indicates the name of GO items, the Y-axis reflects the percentage of genes, the grape area represents biological process clustering, the blue represents cellular component clustering, the red signifies molecular function clustering; c the prediction result of miRNAs regulating GREM1 gene; the four different color ellipses represent the number of miRNAs regulating GREM1 in miRDB, mirDIP, DIANA, and miRNApath databases, and the overlapping section represents the intersection of each other, the central part represents the common intersection of 4 databases. miR-137 microRNA-137, CC cervical cancer, GREM1 gremlin-1, GO gene ontology, DEGs differentially expressed genes

Fig 3: GREM1 is a target gene of miR-137. a Prediction of binding sites between miR-137 and GREM1 identified by bioinformatics website; b, c dual-luciferase reporter assay for confirmation of the targeting relationship between miR-137 and GREM1; *p < 0.05 vs. the NC group; statistical data were presented as mean ± standard deviation; data between two groups were analyzed by paired t-test; one-way analysis of variance was used for multi-group comparisons; the experiment was repeated 3 times independently. GREM1 gremlin-1, miR-137 microRNA-137, NC negative control

Fig 4: Overexpression of miR-137 inhibits CC cell invasion and migration by binding to GREM1. a Cell invasion images using Transwell assay (×200); b statistical results of the number of invading cells of Transwell; c cell migration distance at 24 h and 48 h (×200); d statistical results of the migration distance; *p < 0.05 vs. the blank and NC group; statistical data were presented as mean ± standard deviation; one-way analysis of variance was used for multi-group comparisons; the experiment was repeated 3 times independently. CC cervical cancer, GREM1 gremlin-1, miR-137 microRNA-137

Fig 5: Overexpression of miR-137 inhibits tumor growth by binding to GREM1 in vivo. a The tumor volume changes in nude mice; b representative tumor images and weight of nude mice in each group; c The tumor weight changes in nude mice; *p < 0.05 vs. the blank and NC groups; statistical data were presented as mean ± standard deviation; one-way analysis of variance was used for multi-group comparisons; the experiment was repeated 3 times independently. GREM1 gremlin-1, miR-137 microRNA-137, NC negative control