High miR-31-5p expression promotes colon adenocarcinoma progression by targeting TNS1

Abstract

Overexpression of the miR-31-5p contributes to tumorigenesis and metastasis in diverse neoplasms. In this study, we evaluated expression of miR-31-5p in patients with colon adenocarcinoma (COAD). We found that miR-31-5p was overexpressed in four cohorts (GSE30454, GSE41655, GSE18392, GSE108153) of COAD patients. Importantly, a LinkedOmics analysis revealed that high miR-31-5p expression was associated with poor overall survival of COAD patients. At total of 133 putative target genes of miR-31-5p were identified from TargetScan, miRDB, and TargetMiner. After integrating the target genes with 1,556 deregulated genes in COAD, 8 were acquired that may be targeted by miR-31-5p and contribute to COAD progression. Among these, tensin 1 (TNS1) showed the greatest prognostic ability in COAD and was strongly correlated with M2 macrophages, regulatory T cells, and other immune cells. These findings indicate that, in COAD, miR-31-5p is a potential prognostic factor that affects immune infiltration by targeting TNS1.

Keywords: TNS1; colorectal adenocarcinoma; immune profiling; miR-31-5p; tumor microenvironment.

Figure 1

Expression validation of miR-31-5p. (A) Pancancer expression of miR-31-5p in GEDS. (B) Upregulation of miR-31-5p in the microarrays tissues, based on Gene Expression Omnibus (GEO) data sets. Notes: a, GSE18392; b, GSE108153; c, GSE30454; d, GSE41655.

Figure 2

Prognostic value of miR-31-5p and target genes related with COAD. (A, B) Kaplan-Meier curve for miR-31-5p in clinical COAD samples. The P values of the Kaplan-Meier curve for COAD patients and pathologic stage IV COAD patients were 0.091 and 0.017, respectively. (C) Integration of miR-31-5p predictive genes from TargetScan, miRDB, and TargetMiner. (D) The differentially expressed genes in COAD retrieved from GEPIA. The thresholds were set as follows: | Log2 fold change (FC) | ≥ 2 and P value<0.01. (E) Venn diagram for overlap analysis of miR-31-5p target genes related to COAD.

Figure 3

Expression and mutation analysis of miR-31-5p target genes related to COAD. (A) Expression of integrated genes in COAD and normal tissues based on TCGA samples analyzed by the UALCAN database. (B) OncoPrint of integrated gene alterations in COAD. Genomic alterations of the 8 genes are mutually exclusive.

Figure 4

Kaplan-Meier curve and histochemistry for TNS1 in clinical COAD samples. (A) Kaplan-Meier curve for TNS1 of COAD patients analyzed in the LinkedOmics database. (B) Kaplan-Meier curve for TNS1 of COAD patients analyzed in the UALCAN database. (C) Kaplan-Meier curve for TNS1 of COAD patients analyzed in GEPIA. (D) Kaplan-Meier curve for TNS1 of COAD patients analyzed in the PrognoScan database. (E) Histochemistry of TNS1 in normal colon and colorectal adenocarcinoma tissues. The expression distribution of TNS1 in normal colon tissue and CRC patient samples was evaluated in THPA. Normal HPA036089 (ID1857) and tumor HPA036089 (ID 3550) were presented.

Figure 5

Correlation of TNS1 expression with immune infiltration level in COAD. TNS1 expression is significantly correlated with tumor purity and has strong correlations with macrophages, CD4+ T cells, dendritic cells, and neutrophils.

Figure 6

Correlation of TNS1 expression with immune infiltration level in COAD. TNS1 is closely related with abundance of T cells and has a stronger relationship with macrophage M2 cells than M1 cells.