title: Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis.
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.
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Einav
authors: E
authors: Shoshan
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Aaron K
authors: AK
authors: Mobley
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Russell R
authors: RR
authors: Braeuer
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Takafumi
authors: T
authors: Kamiya
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Li
authors: L
authors: Huang
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Mayra E
authors: ME
authors: Vasquez
authors: The University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, Texas 77030, USA.
authors: Ahmad
authors: A
authors: Salameh
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Ho Jeong
authors: HJ
authors: Lee
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Sun Jin
authors: SJ
authors: Kim
authors: Department of Gynecologic Oncology, Unit 1362, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Cristina
authors: C
authors: Ivan
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Guermarie
authors: G
authors: Velazquez-Torres
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: Ka Ming
authors: KM
authors: Nip
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: Kelsey
authors: K
authors: Zhu
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: Denise
authors: D
authors: Brooks
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: Steven J M
authors: SJ
authors: Jones
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: Inanc
authors: I
authors: Birol
authors: Institute of Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Maribel
authors: M
authors: Mosqueda
authors: Institute of Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Yu-ye
authors: YY
authors: Wen
authors: Institute of Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Agda Karina
authors: AK
authors: Eterovic
authors: 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.
authors: Anil K
authors: AK
authors: Sood
authors: Department of Melanoma Medical Oncology, Unit 0430, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Patrick
authors: P
authors: Hwu
authors: Department of Surgical Oncology, Unit 1484, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Jeffrey E
authors: JE
authors: Gershenwald
authors: Canada's Michael Smith Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.
authors: A Gordon
authors: AG
authors: Robertson
authors: Department of Experimental Therapeutics, Unit 1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: George A
authors: GA
authors: Calin
authors: 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.
authors: Gal
authors: G
authors: Markel
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Isaiah J
authors: IJ
authors: Fidler
authors: Department of Cancer Biology, Unit 0173, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors: Menashe
authors: M
authors: Bar-Eli
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007288:Inosine / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C490386:CPEB1 protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C583404:MIRN455 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D007288:Inosine; D008156:Luciferases; C000595356:ADAR protein, human; D000243:Adenosine Deaminase; D000241:Adenosine