Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach

Abstract

Background Liver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application. Methodology The Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped. Results There were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/

Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3

“…Previous studies have revealed that miR-576-5p plays an important role in CRC metastases. Compared with primary CRC tumors, miR-576-5p is significantly downregulated in the most common liver-metastatic carcinomas and is expressed at high levels in rare brain-metastatic carcinomas 14 , 15 . However, there is little research on the mechanism of miR-576-5p in CRC, which is worthy of further exploration.…”

WITHDRAWN: A Novel Long Non-coding RNA, ENSG00000236199, Inhibits Proliferation and Metastasis through NRIP1 by Sponging miR-576-5p in Hepatocellular Carcinoma

“…In the past, miRNAs were also considered as non-functional RNA, but more and more studies have shown that miRNAs are involved in various biological functions of cells (Tarallo et al 2019;Xu et al 2020;Vignard et al 2020). Many studies have shown that miRNA-576-5p plays an important role in a variety of cancers, such as esophageal cancer (Zhang et al 2019), colorectal cancer (Makondi et al 2019) and melanoma (Kordaß et al 2018).…”

Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

“…Rarely a single miRNA is recognized as a specific biomarker. Recently, miR-576-5p and miR-20a have been identified as individual classifiers in CRC patients who may develop liver metastases, but the combination of the two, or better yet six, miRNAs has offered a far more effective model [13]. The mechanisms that control the progression of CRC may depend on the deregulation of multiple miRNAs resulting in complex dysfunction of cellular molecular networks.…”