PXD002565

PXD002565 is an original dataset announced via ProteomeXchange.

Title	Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy
Description	Focal amplifications of 3p13-3p14 occur in about 10% of melanoma and are associated with poor prognosis. The melanoma-specific oncogene MITF resides at the epicenter of this amplicon1 . However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA gene LINC01212 is consistently cogained with MITF. In addition to being amplified, LINC01212 is a target of the lineage-specific transcription factor SOX10 and, consequently, it is expressed in more than 90% of human melanomas, but not in normal adult tissues. Whereas exogenous LINC01212 functions in trans to increase melanoma clonogenic potential, LINC01212 knock-down drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state, BRAF, NRAS or TP53 status and increases their sensitivity to MAPK-targeting therapeutics both in vitro and in Patient-Derived Xenograft (PDX) models. Mechanistically, LINC01212 interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that targeting the lineage addiction oncogene LINC01212, especially in combination with BRAFV600Einhibitors, disrupts vital mitochondrial functions in a cancer-cell specific manner and is therefore expected to deliver highly effective and tissuerestricted anti-melanoma therapeutic responses.
HostingRepository	PRIDE
AnnounceDate	2016-01-13
AnnouncementXML	Submission_2016-04-05_09:18:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD002565
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sven Eyckerman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide: 15.994915; 2-pyrrolidone-5-carboxylic acid (Gln): -17.026549; monohydroxylated lysine: 15.994915; N-acetylated residue: 42.010565
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-20 06:50:04	ID requested
1	2016-01-13 09:17:25	announced
⏵ 2	2016-04-05 09:18:03	announced	Updated publication reference for PubMed record(s): 27008969.

Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, Radaelli E, Eyckerman S, Leonelli C, Vanderheyden K, Rogiers A, Hermans E, Baatsen P, Aerts S, Amant F, Van Aelst S, van den Oord J, de Strooper B, Davidson I, Lafontaine DL, Gevaert K, Vandesompele J, Mestdagh P, Marine JC, Melanoma addiction to the long non-coding RNA SAMMSON. Nature, 531(7595):518-22(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: lncRNA protein binding melanoma

Kris Gevaert
contact affiliation	Medical Biotechnology Center, VIB, Ghent, Belgium. Department of Biochemistry, Ghent University, Ghent, Belgium;
contact email	kris.gevaert@vib-ugent.be
lab head
Sven Eyckerman
contact affiliation	Medical Protein Research
contact email	sven.eyckerman@vib-ugent.be
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/01/PXD002565

PRIDE project URI

• PRIDE
  1. PXD002565
     1. Label: PRIDE project
     2. Name: Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy