1. MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)
- Author
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Ingvar Syk, Raed Madhi, Anwar Algaber, Amr A. Al-Haidari, and Henrik Thorlacius
- Subjects
0301 basic medicine ,Cancer Research ,Transcription, Genetic ,Colorectal cancer ,Biology ,Transfection ,Culture Media, Serum-Free ,ELAV-Like Protein 1 ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Humans ,Neoplasm Metastasis ,RNA Processing, Post-Transcriptional ,Post-transcriptional regulation ,Regulation of gene expression ,Gene knockdown ,Cancer ,Cell migration ,medicine.disease ,digestive system diseases ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,Oncology ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,5' Untranslated Regions ,HT29 Cells - 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 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.
- Published
- 2018