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MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)

Al-Haidari, Amr LU ; Algaber, Anwar LU ; Madhi, Raed LU ; Syk, Ingvar LU and Thorlacius, Henrik LU (2018) In Cancer Letters 421. p.145-151
Abstract

Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. Bioinformatics analysis predicted two putative binding sites in the AU-rich elements (AREs) at the 3′-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified using specific target site... (More)

Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. Bioinformatics analysis predicted two putative binding sites in the AU-rich elements (AREs) at the 3′-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified using specific target site blockers and functionally validated by use of RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of HuR expression is mediated by AREs. Targeting AREs with a specific blocker inhibited colon cancer cell migration. Taken together, these novel findings demonstrate that AREs mediate miR-155-5p positive regulation of HuR mRNA levels and translation as well as migration in colon cancer cells, suggesting that targeting miR-155-5p and/or Hur might be useful therapeutic strategies against colon cancer metastasis.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell migration, Colon cancer, HuR, Metastasis, microRNA
in
Cancer Letters
volume
421
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:85042429172
ISSN
0304-3835
DOI
10.1016/j.canlet.2018.02.026
language
English
LU publication?
yes
id
e3b33223-02a6-4390-a39b-e9d50cf8f503
date added to LUP
2018-03-17 18:44:17
date last changed
2018-07-08 04:30:37
@article{e3b33223-02a6-4390-a39b-e9d50cf8f503,
  abstract     = {<p>Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. Bioinformatics analysis predicted two putative binding sites in the AU-rich elements (AREs) at the 3′-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified using specific target site blockers and functionally validated by use of RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of HuR expression is mediated by AREs. Targeting AREs with a specific blocker inhibited colon cancer cell migration. Taken together, these novel findings demonstrate that AREs mediate miR-155-5p positive regulation of HuR mRNA levels and translation as well as migration in colon cancer cells, suggesting that targeting miR-155-5p and/or Hur might be useful therapeutic strategies against colon cancer metastasis.</p>},
  author       = {Al-Haidari, Amr and Algaber, Anwar and Madhi, Raed and Syk, Ingvar and Thorlacius, Henrik},
  issn         = {0304-3835},
  keyword      = {Cell migration,Colon cancer,HuR,Metastasis,microRNA},
  language     = {eng},
  month        = {05},
  pages        = {145--151},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)},
  url          = {http://dx.doi.org/10.1016/j.canlet.2018.02.026},
  volume       = {421},
  year         = {2018},
}