The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma

Sanlorenzo, Martina; Vujic, Igor; Esteve-Puig, Rosaura; Lai, Kevin; Vujic, Marin; Lin, Kevin; Posch, Christian; Dimon, Michelle; Moy, Adrian; Zekhtser, Mitchell; Johnston, K.; Gho, Deborah; Ho, Won‐Kyung; Gajjala, Abhinay; Prieto, Juan Oses; Burlingame, Alma L.; Daud, Adil; Rappersberger, Klemens; Ortiz‐Urda, Susana

doi:10.1038/s41598-018-27643-3

Cited by 26 publications

(23 citation statements)

References 47 publications

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“…IQGAP1 has also been reported to play important roles in regulating the microtubule network, actin cytoskeleton and cell adhesion 9 . IQGAP1 has been demonstrated to be regulated by miR-23b cluster, miR-125a-5p 25 , Long noncoding RNA (MIRAT) 26 and promote RAS-MAP kinase-driven cancer invasion 27 . In addition, a significant increase in angiogenesis by the overexpression of IQGAP1 was found in an in vivo mouse model of breast cancer 28 .…”

Section: Discussionmentioning

confidence: 99%

IQGAP1 promotes pancreatic cancer progression and epithelial-mesenchymal transition (EMT) through Wnt/β-catenin signaling

Wang

Zhang

et al. 2019

Sci Rep

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IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a scaffold protein that participates in several cellular functions, including cytoskeletal regulation, cell adhesion, gene transcription and cell polarization. IQGAP1 has been implicated in the tumorigenesis and progression of several human cancers. However, the role of IQGAP1 in pancreatic ductal adenocarcinoma (PDAC) is still unknown. We found that IQGAP1 expression was an independent prognostic factor for PDAC. IQGAP1 upregulation significantly promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas IQGAP1 downregulation impaired its oncogenic functions. Overexpression of IQGAP1 increased the protein level of Dishevelled2 (DVL2) and enhanced canonical Wnt signaling as evidenced by increased DVL2 level, β-catenin transcriptional activity, β-catenin nuclear translocation and expression of the direct target genes of β-catenin (cyclin D1 and c-myc). In contrast, knockdown of IQGAP1 decreased the level of DVL2 and attenuated Wnt/β-catenin signaling. In vivo results revealed that IQGAP1 promoted tumor growth and metastasis. Co-immunoprecipitation studies demonstrated that IQGAP1 interacted with both DVL2 and β-catenin. Moreover, knockdown of DVL2 reversed IQGAP1-induced EMT. Our findings thus confirmed that IQGAP1 could be used as a potential target for PDAC treatment.

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Section: Discussionmentioning

confidence: 99%

IQGAP1 promotes pancreatic cancer progression and epithelial-mesenchymal transition (EMT) through Wnt/β-catenin signaling

Wang

Zhang

et al. 2019

Sci Rep

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“…MAPK Inhibitor Resistance Associated Transcript (MIRAT), a cytoplasmic intergenic lncRNA, functions by binding to the scaffold protein IQ motif containing GTPase activating protein 1 IQGAP1 [ 51 ], a protein facilitating MEK/ERK pathway signaling. MIRAT stabilizes IQGAP1 and inhibits its decay [ 91 , 92 ].…”

Section: Protein-lncrna Interactions In Melanomamentioning

confidence: 99%

The Functional Role of Long Non-Coding RNAs in Melanoma

Wozniak

Czyż

2021

Cancers

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Melanoma is the most lethal skin cancer, with increasing incidence worldwide. The molecular events that drive melanoma development and progression have been extensively studied, resulting in significant improvements in diagnostics and therapeutic approaches. However, a high drug resistance to targeted therapies and adverse effects of immunotherapies are still a major challenge in melanoma treatment. Therefore, the elucidation of molecular mechanisms of melanomagenesis and cancer response to treatment is of great importance. Recently, many studies have revealed the close association of long noncoding RNAs (lncRNAs) with the development of many cancers, including melanoma. These RNA molecules are able to regulate a plethora of crucial cellular processes including proliferation, differentiation, migration, invasion and apoptosis through diverse mechanisms, and even slight dysregulation of their expression may lead to tumorigenesis. lncRNAs are able to bind to protein complexes, DNA and RNAs, affecting their stability, activity, and localization. They can also regulate gene expression in the nucleus. Several functions of lncRNAs are context-dependent. This review summarizes current knowledge regarding the involvement of lncRNAs in melanoma. Their possible role as prognostic markers of melanoma response to treatment and in resistance to therapy is also discussed

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“…On the other hand, the specific silencing of the MIRAT lncRNA in such resistant cells restores sensitivity to MEK inhibitors. Authors suggested that MIRAT lncRNA binds to IQGAP1—boosting MEK to ERK signaling and hyper-activation in different cancer types—and stabilizes it, thus pushing MAPK signaling [ 34 ].…”

Section: Prognostic Value Of Lncrnas In Cutaneous Melanoma and Thementioning

confidence: 99%

Comprehensive Review on the Clinical Relevance of Long Non-Coding RNAs in Cutaneous Melanoma

Falco

Napolitano

Esposito

et al. 2021

IJMS

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Cutaneous melanoma is considered a rare tumor, although it is one of the most common cancers in young adults and its incidence has risen in the last decades. Targeted therapy, with BRAF and MEK inhibitors, and immunotherapy revolutionized the treatment of metastatic melanoma but there is still a considerable percentage of patients with primary or acquired resistance to these therapies. Recently, oncology researchers directed their attention at the role of long non-coding RNAs (lncRNAs) in different types of cancers, including melanoma. lncRNAs are RNA transcripts, initially considered “junk sequences”, that have been proven to have a crucial role in the fine regulation of physiological and pathological processes of different tissues. Furthermore, they are more expressed in tumors than protein-coding genes, constituting perfect candidates either as biomarkers (diagnostic, prognostic, predictive) or as therapeutic targets. In this work, we reviewed all the literature available for lncRNA in melanoma, elucidating all the potential roles in this tumor.

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The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma

Cited by 26 publications

References 47 publications

IQGAP1 promotes pancreatic cancer progression and epithelial-mesenchymal transition (EMT) through Wnt/β-catenin signaling

IQGAP1 promotes pancreatic cancer progression and epithelial-mesenchymal transition (EMT) through Wnt/β-catenin signaling

The Functional Role of Long Non-Coding RNAs in Melanoma

Comprehensive Review on the Clinical Relevance of Long Non-Coding RNAs in Cutaneous Melanoma

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