MicroRNA hsa-let-7e-5p as a potential prognosis marker for rectal carcinoma with liver metastases

Abstract

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that target mRNAs for translational repression or cleavage. The present study was conducted to identify differentially expressed miRNAs in primary tumor tissues of rectal carcinoma (RC) that may be associated with heterochrony hepatic metastasis (HHM). Samples were collected exclusively from patients with RC but not colon cancer (CC); Next-generation high-throughput sequencing technology and bioinformatics tools were used to profile and analyze small RNAs and their corresponding targets in primary tumor tissues with HHM (n=2) or without metastases (non-metastatic, NM; n=2). A total of 24 known miRNAs were identified to be differentially expressed (P<0.01; absolute value of log-fold change ≥1). Hsa-let-7e-5p exhibited the most significant elevation in tissues with HHM (log-fold change=2.62). By combining online informatics resources and previous mRNA sequencing data, it was identified that 54 validated target genes of let-7e were downregulated in primary tumor tissues with HHM. A number of these target genes have been demonstrated to be directly involved in tumor metastasis (including MYC proto-oncogene, bHLH transcription factor, high-mobility group AT-Hook 2, peptidase inhibitor 3, KIT proto-oncogene receptor tyrosine kinase, Jun proto-oncogene, AP-1 transcription factor subunit and ribonuclease T2), or have physiological associations to immunity (including C-C motif chemokine receptor 4 and cluster of differentiation 40 ligand) and cellular metabolism (including peroxisome proliferator-activated receptor γ, coactivator 1 α). Next, 14 target genes were selected for reverse transcription-quantitative polymerase chain reaction analysis in non-sequenced samples, and the downregulation of 10 target genes in RC samples with HHM was confirmed. In addition, it was demonstrated that hsa-let-7e-5p stimulated colorectal cancer cell migration . The miRNA hsa-let-7e-5p may serve as a potential biomarker for rectal carcinoma-associated HHM, facilitating the identification of patients with RC who are at risk of developing HHM.

Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

“…Both HIF-1 signaling [13,14] and cAMP signaling [15] have previously been linked to poor outcomes in gastric cancer, likely due to an increase in the invasiveness of gastric cancer cells. Interestingly, the lower expression of hsa-miR-7704 is already known to be associated with more advanced stages of gastric cancer and a higher risk of liver metastasis in rectal cancer [16,17]. These results are particularly encouraging in light of the numerous studies describing the potential of noncoding RNA species to predict tumor aggressiveness and patient outcome [3].…”

Discovery of inflammatory bowel disease-associated miRNAs using a novel bipartite clustering approach

“…Expression of hsa-let-7e-5p is markedly upregulated in HHM RC. Subsequent assessment of the expression of hsa-let-7e-5p target genes implicated that it may be a prognostic biomarker for RC with HHM [39]. Both inflamed and non-inflamed terminal ileal mucosa in adult patients with active CD have their distinct miRNA expression patterns compared with healthy controls for hsa-let-7b-5p [40].…”

Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

“…Among the miRNAs herein detected, let-7e-5p is broadly described in several cancers, including head and neck and rectum [ 25 , 40 ]. Interestingly, let-7e-5p was suggested as a prognostic marker for inducing metastatic capacity in rectal carcinomas [ 25 ].…”

“…Although many studies propose detecting miRNA signatures for early CRC diagnosis [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ], several limitations are observed, such as reduced coverage for miRNA screening [ 19 , 22 ], variable signatures for different disease stages [ 24 ], absence of non-cancer groups [ 20 ], or lack of data validation. Additionally, some of these studies analyzed only one miRNA as a biomarker [ 25 ], miRNA allied with inflammatory mediators [ 23 ], or miRNA expression without testing the signature’s power [ 18 , 21 , 26 , 27 , 28 ]. Indeed, these strategies have reduced validity due to tumor heterogeneity and potential lack of specificity.…”