A non-coding function of TYRP1 mRNA promotes melanoma growth

Gilot, David; Migault, Mélodie; Bachelot, Laura; Journé, Fabrice; Rogiers, Aljosja; Donnou‐Fournet, Emmanuelle; Mogha, Ariane; Mouchet, Nicolas; Pinel-Marie, Marie-Laure; Mari, Bernard; Montier, Tristan; Corre, Sébastien; Gautron, Arthur; Rambow, Florian; Hajj, Petra El; Jouira, Rania Ben; Tartare‐Deckert, Sophie; Marine, Jean–Christophe; Felden, Brice; Ghanem, Ghanem; Galibert, Marie‐Dominique

doi:10.1038/ncb3623

Cited by 82 publications

(105 citation statements)

References 67 publications

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“…Melanoma cell lines with the highest proliferation rate were among lines expressing TYRP1 transcript at a medium level, whereas those with the highest expression of TYRP1 at the transcript and protein levels exerted one of the lowest proliferation rates. However, our results are in agreement with the findings of Gilot et al [17] when cells lacking detectable TYRP1 protein and expressing TYRP1 mRNA at the level below the median value are exclusively considered. This suggests that GAPDH was used as a loading control.…”

Section: Discussionsupporting

confidence: 93%

“…The high level of TYRP1 mRNA promotes proliferation and tumor growth irrespective of the protein level [17]. In our study, there was no strong association between TYRP1 mRNA level and cell proliferation rate.…”

Section: Discussioncontrasting

confidence: 71%

“…The role of RNAs as endogenous miR sponges has been demonstrated [2,7,19,25,29,39]. TYRP1 mRNA on its non-canonical miRNA response elements can sequester miR-16 and de-repress targets of miR-16 [17]. For the first time, we have shown that the TYRP1 transcript level is not affected during both acute response and development of resistance to vemurafenib and trametinib, which suggests that the role of TYRP1 mRNA as endogenous 'miR sponge' is preserved in resistant cells.…”

Section: Discussionmentioning

confidence: 75%

“…TYRP1 protein expression is reduced in invasive melanomas [4], while TYRP1 mRNA level is increased [28]. TYRP1 mRNA, in addition to the protein-coding function, has been recognized as contributing to regulation of gene expression by serving as an endogenous miR sponge [17].…”

Section: Introductionmentioning

confidence: 99%

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TYRP1 mRNA level is stable and MITF-M-independent in drug-naïve, vemurafenib- and trametinib-resistant BRAFV600E melanoma cells

Hartman

Czyż

2019

Arch Dermatol Res

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TYRP1 mRNA is of interest due to its potential non-coding role as a sponge sequestering tumor-suppressive miRs in melanoma. To our knowledge, there is no report on changes in TYRP1 expression in melanomas after development of resistance to targeted therapies. We used patient-derived drug-naïve RAS Q61R and BRAF V600E melanoma cell lines. In BRAF V600E melanoma cells, resistance to vemurafenib and trametinib was developed. A time-lapse fluorescence microscope was used to rate proliferation, qRT-PCR and Western blotting were used to assess TYRP1 expression and MITF-M level and activity. A high TYRP1 protein level in RAS Q61R cells corresponded with high TYRP1 mRNA level, whereas undetectable TYRP1 protein in BRAF V600E cells was accompanied by medium mRNA level, also in cells carrying NF1 R135W variant in addition. TYRP1 expression was MITF-M-independent, since similar transcript status was found in MITF-M high and MITF-M low cells. For the first time, we showed that TYRP1 expression remained unaltered in melanoma cells that became resistant to vemurafenib or trametinib, including those cells losing MITF-M. Also drug discontinuation in resistant cells did not substantially affect TYRP1 expression. To verify in vitro results, publicly available microarray data were analyzed. TYRP1 transcript levels stay unaltered in the majority of paired melanoma samples from patients before treatment and after relapse caused by resistance to targeted therapies. As TYRP1 mRNA level remains unaltered in melanoma cells during development of resistance to vemurafenib or trametinib, therapies developed to terminate a sponge activity of TYRP1 transcript may be extended to patients that relapse with resistant disease.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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TYRP1 mRNA level is stable and MITF-M-independent in drug-naïve, vemurafenib- and trametinib-resistant BRAFV600E melanoma cells

Hartman

Czyż

2019

Arch Dermatol Res

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“…Gilot et al . reported that the noncoding function of TYRP1 mRNA facilitated melanoma development (Gilot et al , ). Combining the results of previous and current studies, we speculated that the noncoding functions of mRNAs might play an important role in various types of cancer.…”

Section: Discussionmentioning

confidence: 99%

The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17‐RFC2‐5 complex

Wang

Gong

et al. 2020

Molecular Oncology

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Recently, RNAs interacting with proteins have been implicated in playing an important role in the occurrence and progression of oesophageal squamous cell carcinoma (ESCC). In this study, we found that NELFA mRNA interacts with Rad17 through a novel noncoding mode in the nucleus and that the aberrant expression of USF2 contributed to the upregulation of Rad17 and NELFA. Subsequent experiments demonstrated that the deletion of NELFA mRNA significantly decreased ESCC proliferation and colony formation in vitro. Moreover, NELFA mRNA knockdown inhibited DNA damage repair and promoted apoptosis. Mechanistic studies indicated that NELFA mRNA regulated the interaction between Rad17 and RFC2‐5, which had a major impact on the phosphorylation of CHK1, CHK2 and BRCA1. NELFA mRNA expression was consistently elevated in ESCC patients and closely related to decreased overall survival. Taken together, our results confirmed the critical role of the noncoding function of NELFA mRNA in ESCC tumorigenesis and indicated that NELFA mRNA can be regarded as a therapeutic target and an independent prognostic indicator in ESCC patients.

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Interplay between small and long non‐coding RNAs in cutaneous melanoma: a complex jigsaw puzzle with missing pieces

et al. 2018

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The incidence of cutaneous melanoma (CM) has increased in the past few decades. The biology of melanoma is characterized by a complex interaction between genetic, environmental and phenotypic factors. A greater understanding of the molecular mechanisms that promote melanoma cell growth and dissemination is crucial to improve diagnosis, prognostication, and treatment of CM. Both small and long non‐coding RNAs (lncRNAs) have been identified to play a role in melanoma biology; microRNA and lncRNA expression is altered in transformed melanocytes and this in turn has functional effects on cell proliferation, apoptosis, invasion, metastasis, and immune response. Moreover, specific dysregulated ncRNAs were shown to have a diagnostic or prognostic role in melanoma and to drive the establishment of drug resistance. Here, we review the current literature on small and lncRNAs with a role in melanoma, with the aim of putting into some order this complex jigsaw puzzle.

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A non-coding function of TYRP1 mRNA promotes melanoma growth

Cited by 82 publications

References 67 publications

TYRP1 mRNA level is stable and MITF-M-independent in drug-naïve, vemurafenib- and trametinib-resistant BRAFV600E melanoma cells

TYRP1 mRNA level is stable and MITF-M-independent in drug-naïve, vemurafenib- and trametinib-resistant BRAFV600E melanoma cells

The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17‐RFC2‐5 complex

Interplay between small and long non‐coding RNAs in cutaneous melanoma: a complex jigsaw puzzle with missing pieces

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