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Review
. 2018 Nov 22;19(12):3711.
doi: 10.3390/ijms19123711.

The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

Ovidiu Balacescu  1   2 , Daniel Sur  3   4 , Calin Cainap  5   6 , Simona Visan  7 , Daniel Cruceriu  8   9 , Roberta Manzat-Saplacan  10   11 , Mihai-Stefan Muresan  12   13 , Loredana Balacescu  14   15 , Cosmin Lisencu  16   17 , Alexandru Irimie  18   19
Affiliations
Review

The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

Ovidiu Balacescu et al. Int J Mol Sci. .

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial⁻mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

Keywords: colorectal cancer; exosomes; liver; metastases; miRNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The PubMed string searches used to identify the specific miRNAs involved in colorectal cancer (CRC) development and progression as well as in liver metastasis.
Figure 2
Figure 2
MiRNA biogenesis. MiRNA biogenesis starts in the nucleus with a long hairpin transcript called pri-miRNA that is further processed to a smaller transcript of 70 nucleotides. After is exported in the cytoplasm, pre-miRNA is enzymatically processed to single-strand mature miRNA of about 21–23 nucleotides. When it is incorporated in the enzymatically machinery called the RNA-induced silencing complex (RISC), mature miRNA guide the RISC to silence the specific mRNA transcripts, either by their degradation of by translation repression.
Figure 3
Figure 3
CRC metastasis in the liver through CRC circulating tumor cells (CTCs), mediated by miRNAs transported by CRC-delivered exosomes (miRNA-TEX). CXCR4 and CCR6 chemokine receptors are responsible for liver organotropism of miRNA-TEX, while the miRNAs released in the liver are responsible for preparing the secondary pre-metastatic niche by inducing the pro-inflammatory and pro-tumorigenic signals.
See this image and copyright information in PMC

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