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Nat Cell Biol. 2015 Mar;17(3):311-21. doi: 10.1038/ncb3110. Epub 2015 Feb 16.

Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis.

Author information

1
Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
2
The University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, Texas 77030, USA.
3
Department of Gynecologic Oncology, Unit 1362, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
4
Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
5
Institute of Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
6
1] Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA [2] Department of Gynecologic Oncology, Unit 1362, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
7
Department of Melanoma Medical Oncology, Unit 0430, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
8
Department of Surgical Oncology, Unit 1484, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
9
Department of Experimental Therapeutics, Unit 1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
10
1] Ella Institute of Melanoma, Sheba Medical Center, Ramat-Gan 52621, Israel [2] Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

Abstract

Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs (miRNAs), its effects on tumour growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumour specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified three miRNAs undergoing A-to-I editing in the weakly metastatic melanoma but not in strongly metastatic cell lines. One of these miRNAs, miR-455-5p, has two A-to-I RNA-editing sites. The biological function of edited miR-455-5p is different from that of the unedited form, as it recognizes a different set of genes. Indeed, wild-type miR-455-5p promotes melanoma metastasis through inhibition of the tumour suppressor gene CPEB1. Moreover, wild-type miR-455 enhances melanoma growth and metastasis in vivo, whereas the edited form inhibits these features. These results demonstrate a previously unrecognized role for RNA editing in melanoma progression.

Comment in

PMID:
25686251
PMCID:
PMC4344852
DOI:
10.1038/ncb3110
[Indexed for MEDLINE]
Free PMC Article

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