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

Einav Shoshan; Aaron K Mobley; Russell R Braeuer; Takafumi Kamiya; Li Huang; Mayra E Vasquez; Ahmad Salameh; Ho Jeong Lee; Sun Jin Kim; Cristina Ivan; Guermarie Velazquez-Torres; Ka Ming Nip; Kelsey Zhu; Denise Brooks; Steven J M Jones; Inanc Birol; Maribel Mosqueda; Yu-ye Wen; Agda Karina Eterovic; Anil K Sood; Patrick Hwu; Jeffrey E Gershenwald; A Gordon Robertson; George A Calin; Gal Markel; Isaiah J Fidler; Menashe Bar-Eli

doi:10.1038/ncb3110

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

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

Authors

Einav Shoshan¹, Aaron K Mobley¹, Russell R Braeuer¹, Takafumi Kamiya¹, Li Huang¹, Mayra E Vasquez¹, Ahmad Salameh², Ho Jeong Lee¹, Sun Jin Kim¹, Cristina Ivan³, Guermarie Velazquez-Torres¹, Ka Ming Nip⁴, Kelsey Zhu⁴, Denise Brooks⁴, Steven J M Jones⁴, Inanc Birol⁴, Maribel Mosqueda⁵, Yu-ye Wen⁵, Agda Karina Eterovic⁵, Anil K Sood⁶, Patrick Hwu⁷, Jeffrey E Gershenwald⁸, A Gordon Robertson⁴, George A Calin⁹, Gal Markel¹⁰, Isaiah J Fidler¹, Menashe Bar-Eli¹

Affiliations

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.

PMID: 25686251
PMCID: PMC4344852
DOI: 10.1038/ncb3110

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adenosine / metabolism*
Adenosine Deaminase / genetics
Adenosine Deaminase / metabolism
Animals
Base Sequence
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism
Disease Progression
Female
Gene Expression Regulation, Neoplastic*
Genes, Reporter
Humans
Inosine / metabolism*
Luciferases / genetics
Luciferases / metabolism
Melanoma / genetics*
Melanoma / metabolism
Melanoma / pathology
Mice
Mice, Nude
MicroRNAs
Molecular Sequence Data
Neoplasm Metastasis
Neoplasm Transplantation
RNA Editing*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Skin Neoplasms / genetics*
Skin Neoplasms / metabolism
Skin Neoplasms / pathology
Transcription Factors / genetics
Transcription Factors / metabolism
mRNA Cleavage and Polyadenylation Factors / genetics
mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

CPEB1 protein, human
CREB1 protein, human
Cyclic AMP Response Element-Binding Protein
MIRN455 microRNA, human
MicroRNAs
RNA-Binding Proteins
Transcription Factors
mRNA Cleavage and Polyadenylation Factors
Inosine
Luciferases
ADAR protein, human
Adenosine Deaminase
Adenosine

Grants and funding

P50 CA093459/CA/NCI NIH HHS/United States