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

Chen,Wenfeng; Lin,Guosheng; Yao,Yizhou; Chen,Jishen; Shui,Hanli; Yang,Qinghai; Wang,Xiaoya; Weng,Xiaoyuan; Sun,Ling; Chen,Fei; Yang,Sheng; Yang,Yufeng; Zhou,Yongjian

doi:10.3892/ol.2018.8181

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

Authors:
- Wenfeng Chen
- Guosheng Lin
- Yizhou Yao
- Jishen Chen
- Hanli Shui
- Qinghai Yang
- Xiaoya Wang
- Xiaoyuan Weng
- Ling Sun
- Fei Chen
- Sheng Yang
- Yufeng Yang
- Yongjian Zhou
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Affiliations: Institute of Life Sciences, College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, P.R. China, Department of Gastric Surgery, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Department of Molecular Pathology, Fuzhou Maixin Biotech., Co., Ltd., Fuzhou, Fujian 350001, P.R. China
Published online on: March 6, 2018 https://doi.org/10.3892/ol.2018.8181
Pages: 6913-6924
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 log2‑fold change ≥1). Hsa‑let‑7e‑5p exhibited the most significant elevation in tissues with HHM (log2‑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 in vitro. 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.

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