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. 2023 Sep 6:11:1161667.
doi: 10.3389/fcell.2023.1161667. eCollection 2023.

Identification and verification of a prognostic signature based on a miRNA-mRNA interaction pattern in colon adenocarcinoma

Qiwu Zhao #  1 , Haosheng Li #  1 , Wenchang Li #  2 , Zichao Guo  1 , Wenqing Jia  1 , Shuiyu Xu  1 , Sixia Chen  3 , Xiaonan Shen  4 , Changgang Wang  1
Affiliations

Identification and verification of a prognostic signature based on a miRNA-mRNA interaction pattern in colon adenocarcinoma

Qiwu Zhao et al. Front Cell Dev Biol. .

Abstract

The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy.

Keywords: RNA therapy; colon adenocarcinoma; miRNAs; prognostic signature; tissue microarray.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Volcano plot of differently expressed mRNA (A) and miRNA precursors (B).
FIGURE 2
FIGURE 2
Functional enrichment analyses of differentially expressed target genes. (A) Schematic diagram of the process of screening differentially expressed target genes. (B–D) Cellular component (CC), biological processes (BP), and molecular functions (MF) results of GO enrichment analysis. (E) Results of KEGG pathway enrichment analysis.
FIGURE 3
FIGURE 3
Identification and validation of the prognostic signature. (A) Forest plot of the nine-gene signature. (B) Kaplan–Meier survival curves of high- and low-risk groups. (C) ROC curve of this prognostic signature.
FIGURE 4
FIGURE 4
Prognostic effects of nine genes in the model. (A) Kaplan–Meier survival curves of high- and low-expression groups of these nine genes. (B) Nine pairs of signature genes and potential regulatory miRNAs. Red indicates that the expression level of genes or miRNAs was upregulated in COAD, while blue indicates that the expression level of genes or miRNAs was downregulated.
FIGURE 5
FIGURE 5
Immunohistochemical staining of tissue microarrays containing cancer and paired para-cancer normal tissues from 100 patients with COAD.
See this image and copyright information in PMC

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