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Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy

ABSTRACT: Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy

PROVIDER: PRJNA287799 | ENA |

REPOSITORIES: ENA

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Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy [2]

Project 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 co-gained 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 dramatically decreases the viability of melanoma cells irrespective of their transcriptional cell state, BRAF, NRAS or TP53 status, diminishes melanoma growth and increases their sensitivity to MAPK-targeting therapeutics both in vitro and in patient-derived melanoma xenograft mouse models. Mechanistically, LINC01212 functions as a lineage addiction oncogene by interacting with and modulating the cellular localization and function of two proteins, XRN2 and p32, involved in nucleolar and mitochondrial rRNA processing, ribosome biogenesis and protein synthesis. LINC01212 targeting, especially in combination with BRAFV600E-inhibitors, is expected to deliver highly effective and tissue-restricted antimelanoma therapeutic responses. Five GapmeR3 treated and four control treated patient derived xenografts were analysed.

2016-01-15 | E-GEOD-70177 | biostudies-arrayexpress

Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy

Project 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.

2016-01-13 | PXD002565 | Pride

Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy [2]

2016-01-15 | GSE70177 | GEO

Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy [1]

2016-01-15 | GSE70176 | GEO

Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

Project description:Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

| PRJNA991486 | ENA

Targeting the lineage-specific long non-coding RNA LINC01212 as an effective anti-melanoma therapeutic strategy

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-01-15 | GSE70180 | GEO

Disrupting ATF4 expression mechanisms provides an effective strategy for BRAF-targeted melanoma therapy

Project description:Disrupting ATF4 expression mechanisms provides an effective strategy for BRAF-targeted melanoma therapy

| PRJNA562868 | ENA

Wnt activation as a therapeutic strategy in medulloblastoma

Project description:Wnt activation as a therapeutic strategy in medulloblastoma

| PRJNA543788 | ENA

Intraperitoneal paclitaxel is a safe and effective therapeutic strategy for treating mucinous appendiceal adenocarcinoma

Project description:Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal (IP) delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by IP administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly IP paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous (IV) to IP administration, IP delivery of paclitaxel was more effective with reduced systemic side effects in mice. Given the established safety record of IP paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of IP paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of IP paclitaxel in a prospective clinical trial.

2023-07-07 | GSE236502 | GEO

Disrupting ATF4 expression mechanisms provides an effective strategy for BRAF-targeted melanoma therapy (Knockdown Series)

Project description:Disrupting ATF4 expression mechanisms provides an effective strategy for BRAF-targeted melanoma therapy (Knockdown Series)

| PRJNA562870 | ENA