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

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

doi:10.1038/ncb3110

Cited by 217 publications

(218 citation statements)

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“…These effects are mediated by the ability of the edited miRNA to target AMFR combined with an inability to inhibit the original target RAP2A (Choudhury et al 2012). In melanoma, edited miR-455 has been proposed to suppress tumor growth and metastasis by upregulating tumor suppressor CPEB1 (Shoshan et al 2015).…”

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confidence: 99%

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

et al. 2017

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RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.

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confidence: 99%

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

et al. 2017

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“…Liu et al (36) identified that miR-455-5p was associated with anaplastic lymphoma kinase expression. Shoshan et al (37) confirmed that miR-455-5p contributes to melanoma growth and metastasis through the downregulation of the tumor-suppressor gene cytoplasmic polyadenylation element binding protein 1. However, the exact role with respect to influencing cell proliferation and apoptosis, and the regulatory mechanism of miR-455-5p in colon cancer remains unclear.…”

Section: Discussionmentioning

confidence: 88%

miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer

et al. 2017

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Abstract.Although there is evidence that galectin-9 is a critical factor in health and disease, the upstream regulatory microRNA (miRNA or miR) of the protein remains poorly defined. miR-455-5p is characterized as a tumor-associated miRNA in cancer research. However, the actual role of miR-455-5p with respect to inhibiting or promoting tumorigenesis in colon cancer is unclear. The present study aimed to investigate the expression, role and target regulation association of galectin-9 and miR-455-5p in colon cancer. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were used for the detection of the expression levels of galectin-9 and miRNAs. Cell Counting kit-8 test was used for the evaluation of cell proliferation, while flow cytometry was used for cell apoptosis analysis. A potential interaction between galectin-9 and miR-455-5p was predicted by target prediction programs and confirmed by luciferase assay and transfection with miRNA mimics. The present study revealed that elevated expression of galectin-9 and miR-455-5p in colon cancer was associated with HT29 cell proliferation and apoptosis. Furthermore, the present study demonstrated that miR-455-5p reduced galectin-9 expression by directly targeting its 3'-untranslated region. These data suggest that miR-455-5p functions as a potential oncogene in colon cancer by targeting galectin-9.

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“…of Pages 11 in metastatic melanoma cell lines was detected compared to primary tumors or normal melanocytes [69]. A recent paper also demonstrated that ADAR1 downregulation could be regulated by cAMP response element-binding protein (CREB) in metastatic melanoma [70]. In this cellular context, reduced levels of ADAR1 promoted tumor growth and cell proliferation, accompanied by a metastatic phenotype.…”

Section: Reviewmentioning

confidence: 93%

“…RNA editing-independent changes in miRNA expression may occur as a result of direct binding of ADAR1 to pri-miRNA or regulation of the miRNA processing machinery by ADAR1 [69]. Alternatively, RNA editing of three miRNAs, including miR-455-5p, has been reported [70]. Editing events resulted in changes in miRNA processing as well as in miR-455 targeting.…”

Section: Reviewmentioning

confidence: 97%

RNA rewriting, recoding, and rewiring in human disease

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et al. 2015

Trends in Molecular Medicine

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

Cited by 217 publications

References 39 publications

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer

RNA rewriting, recoding, and rewiring in human disease

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