Upregulation of microRNA miR-141-3p and its prospective targets in endometrial carcinoma: a comprehensive study

Figures & data

Figure 1. Screening process for miRNA expression profiles of endometrial carcinoma. GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas

Figure 2. The expression of miR-141-3p in endometrial carcinoma (EC) and corresponding noncancerous tissues . (a, b) Scatter plot and receiver operating characteristic (ROC) curve of in-house quantitative real-time polymerase chain reaction (RT-qPCR). (c, d) Scatter plot and ROC curve of TCGA-UCEC cohort. (e, f) Scatter plot and ROC curve of GSE25405 dataset. (g, h) Scatter plot and ROC curve of GSE35794 dataset. (i) Forest plot of standard mean difference (SMD) of miR-141-3p expression in EC and non-EC groups. (j) Funnel plot of Egger’s test for pubilication bias

Table 1. The charateristics of the four cohorts included in the integrated analysis

Study	Year	Country	Platform	Cancer group	Normal control
GSE25405	2010	Japan	GPL7731	41	7
GSE35794	2012	Polan	GPL10850	18	4
TCGA-UCEC^a	2020	USA	RNA-seq	546	22
RT-qPCR^b	2020	China	RT-qPCR	70	30

Note: a, uterine corpus endometrial carcinoma in The Cancer Genome Atlas; b, quantitative real-time polymerase chain reaction.

Figure 3. Pooled diagnostic indices for the integrated analysis based on four included studies. (a) The pooled sensitivity was 0.84 (0.81– 0.86). (b) The pooled specificity was 0.76 (0.64– 0.85). (c) The pooled positive likelihood ratio (LR) was 3.52 (2.26– 5.47). (d) The pooled negative LR was 0.21 (0.17– 0.27). (e) The pooled diagnostic score was 2.80 (2.18– 3.41). (f) The pooled diagnostic OR was 16.44 (8.89 −30.39)

Figure 4. Summary receiver operating characteristic (sROC) curve of miR-141-3p in endometrial carcinoma (a) and Deek’s funnel plot for the publication bias test (b). Kaplan-Meier curve between the high and low miR-141-3p expression group evaluated the prognostic significance (c)

Figure 5. Venn diagram and genes enrichment analysis. (a) Venn diagram of overlapping predicted and downregulation genes. (b) Gene ontology (GO) term annotation analysis of target genes. (c) The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes

Table 2. KEGG pathway enrichment analysis of miR-141-3p related genes

ID	Term	Count	P value	Genes
hsa04510	Focal adhesion	12	<0.0001	PDGFRA, JUN, PPP1R12A, CCND2, HGF, ITGA11, KDR, PRKCA, PPP1R12B, THBS1, EGFR, VCL
hsa04015	Rap1 signaling pathway	11	<0.0001	PDGFRA, KITLG, CNR1, HGF, MAGI2, KDR, PRKCA, PRKD1, FGF13, THBS1, EGFR
hsa04012	ErbB signaling pathway	7	0.0010	STAT5B, CAMK2D, JUN, GAB1, ABL1, PRKCA, EGFR
hsa05205	Proteoglycans in cancer	10	0.0013	CAMK2D, PPP1R12A, FZD4, HGF, GAB1, KDR, PRKCA, PPP1R12B, THBS1, EGFR
hsa05206	MicroRNAs in cancer	11	0.0047	PDGFRA, ZEB2, ZEB1, CCND2, MMP16, IRS1, ABL1, IRS2, PRKCA, THBS1, EGFR
hsa04151	PI3K-Akt signaling pathway	12	0.0060	PHLPP2, PDGFRA, KITLG, CCND2, IRS1, HGF, ITGA11, KDR, PRKCA, FGF13, THBS1, EGFR
hsa04810	Regulation of actin cytoskeleton	9	0.0068	PDGFRA, PPP1R12A, GSN, CFL2, ITGA11, FGF13, PPP1R12B, EGFR, VCL
hsa04014	Ras signaling pathway	9	0.0104	PDGFRA, KITLG, HGF, GAB1, ABL1, KDR, PRKCA, FGF13, EGFR
hsa05231	Choline metabolism in cancer	6	0.0111	PDGFRA, JUN, DGKE, CHPT1, PRKCA, EGFR
hsa04921	Oxytocin signaling pathway	7	0.0149	CAMK2D, JUN, PPP1R12A, CACNA2D1, PRKCA, PPP1R12B, EGFR
hsa05200	Pathways in cancer	12	0.0152	PDGFRA, STAT5B, JUN, KITLG, CXCL12, FZD4, HGF, ABL1, PRKCA, FGF13, EGFR, GLI2
hsa04722	Neurotrophin signaling pathway	6	0.0219	MAP3K3, CAMK2D, JUN, IRS1, GAB1, ABL1
hsa04912	GnRH signaling pathway	5	0.0332	MAP3K3, CAMK2D, JUN, PRKCA, EGFR
hsa04310	Wnt signaling pathway	6	0.0370	CAMK2D, JUN, CCND2, FZD4, PRKCA, PRICKLE1

Figure 6. Relationship between miR-141-3p and PPP1R12A in endometrial carcinomam (EC). (a) Complementary base sequences of miR-141-3p and PPP1R12A. (b, c) Scatter plot and receiver operating characteristic (ROC) curve of PPP1R12A in EC and non-EC tissues from TCGA-UCEC. (d) Negative correlation between miR-141-3p and PPP1R12A in EC on the basis of starBase v3.0. (e) The expression of PPP1R12A protein in normal glandular cells of uterus endometrium (Female aged 39, patient ID: 4569, antibody HPA071956, high staining). (f) The expression of PPP1R12A protein in EC cells (Female aged 58, patient ID: 2621, antibody HPA071956, staining not dected). (g) The expression of PPP1R12A protein in EC cells (Female aged 79, patient ID: 7339, antibody HPA071956, staining not dected)

Figure 7. Relationship between miR-141-3p and PPP1R12B in endometrial carcinomam (EC). (a) Complementary base sequences of miR-141-3p and PPP1R12B. (b, c) Scatter plot and receiver operating characteristic (ROC) curve of PPP1R12B in EC and non-EC tissues from TCGA-UCEC. (d) Negative correlation between miR-141-3p and PPP1R12B in EC on the basis of starBase v3.0. (e) The expression of PPP1R12B protein in normal glandular cells of uterus endometrium (Female aged 51, patient ID: 3491, antibody HPA024640, low staining). (f) The expression of PPP1R12B protein in EC cells (Female aged 70, patient ID: 2118, antibody HPA024640, staining not dected). (g) The expression of PPP1R12B protein in EC cells (Female aged 51, patient ID: 3481, antibody HPA024640, staining not dected)

Data availability statement:

Not applicable.