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Published in: BMC Cancer 1/2021

01-12-2021 | Metastasis | Research

The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p

Authors: Heyang Xu, Qiusheng Lan, Yongliang Huang, Yang Zhang, Yujie Zeng, Pengwei Su, Ziqiang Chu, Wei Lai, Zhonghua Chu

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear.

Methods

Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET.

Results

In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells.

Coclusion

MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.
Literature
5.
go back to reference Zeisberg M, Shah AA, Kalluri R. Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem. 2015;280:8094–100.CrossRef Zeisberg M, Shah AA, Kalluri R. Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem. 2015;280:8094–100.CrossRef
16.
go back to reference Epstein DM, Buck E. Old dog, new tricks: extracellular domain arginine methylation regulates EGFR function. J Clin Invest. 2014;125:4320–2.CrossRef Epstein DM, Buck E. Old dog, new tricks: extracellular domain arginine methylation regulates EGFR function. J Clin Invest. 2014;125:4320–2.CrossRef
20.
go back to reference Yates CC, Shepard CR, Stolz DB, Wells A. Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer. 2011;96:1246–52.CrossRef Yates CC, Shepard CR, Stolz DB, Wells A. Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer. 2011;96:1246–52.CrossRef
28.
go back to reference Vu T, Datta PK. Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis. Cancers (Basel). 2017;9(12):171 Vu T, Datta PK. Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis. Cancers (Basel). 2017;9(12):171
33.
go back to reference Forte E, Orsatti L, Talamo F, Barbato G, De Francesco R, Tomei L. Ezrin is a specific and direct target of protein tyrosine phosphatase PRL-3. Biochim Biophys Acta. 1783;2008:334–44. Forte E, Orsatti L, Talamo F, Barbato G, De Francesco R, Tomei L. Ezrin is a specific and direct target of protein tyrosine phosphatase PRL-3. Biochim Biophys Acta. 1783;2008:334–44.
34.
go back to reference Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM. Directional cell movement through tissues is controlled by exosome secretion. Nat Commun. 2005;6:7164.CrossRef Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM. Directional cell movement through tissues is controlled by exosome secretion. Nat Commun. 2005;6:7164.CrossRef
37.
go back to reference Hou Y, Hu Q, Huang J, Xiong H. Omeprazole inhibits cell proliferation and induces G0/G1 cell cycle arrest through up-regulating miR-203a-3p expression in Barrett's esophagus cells. Front Pharmacol. 2017;8:968.CrossRefPubMed Hou Y, Hu Q, Huang J, Xiong H. Omeprazole inhibits cell proliferation and induces G0/G1 cell cycle arrest through up-regulating miR-203a-3p expression in Barrett's esophagus cells. Front Pharmacol. 2017;8:968.CrossRefPubMed
38.
go back to reference Lin C, Gao H, Liang J, et al. MiR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D. Am J Cancer Res. 2018;8(12):2387–401. Lin C, Gao H, Liang J, et al. MiR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D. Am J Cancer Res. 2018;8(12):2387–401.
41.
go back to reference Rivard N. Phosphatidylinositol 3-kinase: a key regulator in adherens junction formation and function. Front Biosci (Landmark Ed). 2009;14:510–22.CrossRef Rivard N. Phosphatidylinositol 3-kinase: a key regulator in adherens junction formation and function. Front Biosci (Landmark Ed). 2009;14:510–22.CrossRef
Metadata
Title
The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p
Authors
Heyang Xu
Qiusheng Lan
Yongliang Huang
Yang Zhang
Yujie Zeng
Pengwei Su
Ziqiang Chu
Wei Lai
Zhonghua Chu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08419-x

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