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MiR-155-5p positively regulates CCL17-induced colon cancer cell migration by targeting RhoA

Al-Haidari, Amr A. LU ; Syk, Ingvar LU and Thorlacius, Henrik LU (2017) In Oncotarget 8(9). p.14887-14896
Abstract

Colorectal cancer is the second most common cause of cancer-related death, which is due to migration of tumor cells to distant sites of metastasis. Accumulating data indicate that mciroRNAs play an important role in several aspects of colon cancer cell biology. Herein, we examined the role of miR-155-5p in colon cancer cell migration induced by the CCL17-CCR4 axis in HT-29 colon cancer cells. We found that miR-155-5p knockdown in serum starved colon cancer cells decreased CCL17-induced cell chemotaxis. Moreover, knocking down miR-155-5p markedly decreased CCL17-provoked activation of RhoA in colon cancer cells. Bioinformatics analysis predicted two putative binding sites in the AU-rich element at the 3'-UTR of RhoA mRNA. MiR-155-5p... (More)

Colorectal cancer is the second most common cause of cancer-related death, which is due to migration of tumor cells to distant sites of metastasis. Accumulating data indicate that mciroRNAs play an important role in several aspects of colon cancer cell biology. Herein, we examined the role of miR-155-5p in colon cancer cell migration induced by the CCL17-CCR4 axis in HT-29 colon cancer cells. We found that miR-155-5p knockdown in serum starved colon cancer cells decreased CCL17-induced cell chemotaxis. Moreover, knocking down miR-155-5p markedly decreased CCL17-provoked activation of RhoA in colon cancer cells. Bioinformatics analysis predicted two putative binding sites in the AU-rich element at the 3'-UTR of RhoA mRNA. MiR-155-5p binding to RhoA mRNA was verified using a target site blocker and functionally validated by RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of RhoA mRNA is mediated by AU-rich elements present in the 3'-UTR region. Taken together, these results show that miR-155-5p positively regulates RhoA mRNA levels and translation as well as cell migration in serum starved colon cancer cells and indicate that targeting miR-155-5p might be a useful strategy to antagonize colon cancer metastasis.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Chemokines, Chemotaxis, Colon cancer, Metastasis, MicroRNA
in
Oncotarget
volume
8
issue
9
pages
10 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85014117846
  • wos:000396013700055
ISSN
1949-2553
DOI
10.18632/oncotarget.14841
language
English
LU publication?
yes
id
24ab015f-7a4d-4b70-9fde-2b13658eae01
date added to LUP
2017-03-24 11:41:04
date last changed
2018-01-07 11:56:53
@article{24ab015f-7a4d-4b70-9fde-2b13658eae01,
  abstract     = {<p>Colorectal cancer is the second most common cause of cancer-related death, which is due to migration of tumor cells to distant sites of metastasis. Accumulating data indicate that mciroRNAs play an important role in several aspects of colon cancer cell biology. Herein, we examined the role of miR-155-5p in colon cancer cell migration induced by the CCL17-CCR4 axis in HT-29 colon cancer cells. We found that miR-155-5p knockdown in serum starved colon cancer cells decreased CCL17-induced cell chemotaxis. Moreover, knocking down miR-155-5p markedly decreased CCL17-provoked activation of RhoA in colon cancer cells. Bioinformatics analysis predicted two putative binding sites in the AU-rich element at the 3'-UTR of RhoA mRNA. MiR-155-5p binding to RhoA mRNA was verified using a target site blocker and functionally validated by RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of RhoA mRNA is mediated by AU-rich elements present in the 3'-UTR region. Taken together, these results show that miR-155-5p positively regulates RhoA mRNA levels and translation as well as cell migration in serum starved colon cancer cells and indicate that targeting miR-155-5p might be a useful strategy to antagonize colon cancer metastasis.</p>},
  author       = {Al-Haidari, Amr A. and Syk, Ingvar and Thorlacius, Henrik},
  issn         = {1949-2553},
  keyword      = {Chemokines,Chemotaxis,Colon cancer,Metastasis,MicroRNA},
  language     = {eng},
  number       = {9},
  pages        = {14887--14896},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {MiR-155-5p positively regulates CCL17-induced colon cancer cell migration by targeting RhoA},
  url          = {http://dx.doi.org/10.18632/oncotarget.14841},
  volume       = {8},
  year         = {2017},
}