LADON, a Natural Antisense Transcript of NODAL, Promotes Tumour Progression and Metastasis in Melanoma.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Annie Dutriaux, Serena Diazzi, Chiara Bresesti, Sylvie Hardouin, Frédérique Deshayes, Jérôme Collignon, Domenico Flagiello
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引用次数: 0

Abstract

The TGFβ family member NODAL, repeatedly required during embryonic development, has also been associated with tumour progression. Our aim was to clarify the controversy surrounding its involvement in melanoma tumour progression. We found that the deletion of the NODAL exon 2 in a metastatic melanoma cell line impairs its ability to form tumours and colonize distant tissues. However, we show that this phenotype does not result from the absence of NODAL, but from a defect in the expression of a natural antisense transcript of NODAL, here called LADON. We show that LADON expression is specifically activated in metastatic melanoma cell lines, that its transcript is packaged in exosomes secreted by melanoma cells, and that, via its differential impact on the expression of oncogenes and tumour suppressors, it promotes the mesenchymal to amoeboid transition that is critical for melanoma cell invasiveness. LADON is, therefore, a new player in the regulatory network governing tumour progression in melanoma and possibly in other types of cancer.

LADON是一种天然的NODAL反义转录物,促进黑色素瘤的肿瘤进展和转移。
TGFβ家族成员NODAL在胚胎发育过程中反复需要,也与肿瘤进展有关。我们的目的是澄清围绕其参与黑色素瘤进展的争议。我们发现转移性黑色素瘤细胞系中NODAL外显子2的缺失会损害其形成肿瘤和定植远端组织的能力。然而,我们发现这种表型不是由于缺乏NODAL,而是由于NODAL的自然反义转录物(这里称为LADON)的表达缺陷。我们发现LADON的表达在转移性黑色素瘤细胞系中被特异性激活,其转录物被包装在黑色素瘤细胞分泌的外泌体中,并且通过其对癌基因和肿瘤抑制因子表达的差异影响,它促进了间充质向变形虫的转化,这对黑色素瘤细胞的侵袭性至关重要。因此,LADON在控制黑色素瘤和其他类型癌症的肿瘤进展的调节网络中是一个新的参与者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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