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Article: MiR-122-5p expression and secretion in melanoma cells is amplified by the LPAR3 SH3–binding domain to regulate WNT1

TitleMiR-122-5p expression and secretion in melanoma cells is amplified by the LPAR3 SH3–binding domain to regulate WNT1
Authors
Issue Date2019
Citation
Molecular Cancer Research, 2019, v. 17, n. 1, p. 299-309 How to Cite?
AbstractThe lysophosphatidic acid receptor-3 (LPAR3) is a G protein–coupled receptor that mediates viability among malignant cells and aggressiveness among certain tumors. The study's objective was to determine the interplay between LPAR3 and miRNAs to impact key cellular signaling pathways. Using SK-Mel-2 and SK-Mel-5 melanoma cells, wild-type and mutated receptors were stably expressed to explore molecular mechanisms. LPAR3 signaling induced miR-122-5p intracellularly and subsequently its inclusion into exosomes. This amplification resulted in less abundant Wnt1, maintenance of GSK3 inactivation and to a lesser extent, partial degradation of b-catenin. The surge in miR-122-5p and reduction in Wnt1 originated from signaling at the Src homology 3 (SH3) ligand–binding motif within the third intracellular loop of LPAR3, because mutant receptors did not increase miR-122-5p and had a weakened capacity to reduce Wnt1. In addition, a key mediator of melanoma survival signaling, the peroxisome proliferator-activated receptor gamma coactivator 1-a (PPARGC1A/PGC1), was involved in miR-122-5p transcription. In conclusion, this study highlights the powerful role miRNAs have in fine-tuning specific G protein–coupled receptor-mediated signaling events by altering the transcription of signaling transduction pathway components. This study also identifies that LPAR3 increases miR-122-5p expression, which occurs mechanistically through the SH3 domain and helps explain why miR-122-5p increases are detected in cancer patient serum. Implications: LPAR3 is partially responsible for the production and secretion of miR-122-5p, found in the serum of a wide variety of patients with cancer.
Persistent Identifierhttp://hdl.handle.net/10722/342708
ISSN
2023 Impact Factor: 4.1
2023 SCImago Journal Rankings: 1.660
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorByrnes, Charnel C.-
dc.contributor.authorJia, Wei-
dc.contributor.authorAlshamrani, Ali A.-
dc.contributor.authorKuppa, Sudeepti S.-
dc.contributor.authorMurph, Mandi M.-
dc.date.accessioned2024-04-17T07:05:41Z-
dc.date.available2024-04-17T07:05:41Z-
dc.date.issued2019-
dc.identifier.citationMolecular Cancer Research, 2019, v. 17, n. 1, p. 299-309-
dc.identifier.issn1541-7786-
dc.identifier.urihttp://hdl.handle.net/10722/342708-
dc.description.abstractThe lysophosphatidic acid receptor-3 (LPAR3) is a G protein–coupled receptor that mediates viability among malignant cells and aggressiveness among certain tumors. The study's objective was to determine the interplay between LPAR3 and miRNAs to impact key cellular signaling pathways. Using SK-Mel-2 and SK-Mel-5 melanoma cells, wild-type and mutated receptors were stably expressed to explore molecular mechanisms. LPAR3 signaling induced miR-122-5p intracellularly and subsequently its inclusion into exosomes. This amplification resulted in less abundant Wnt1, maintenance of GSK3 inactivation and to a lesser extent, partial degradation of b-catenin. The surge in miR-122-5p and reduction in Wnt1 originated from signaling at the Src homology 3 (SH3) ligand–binding motif within the third intracellular loop of LPAR3, because mutant receptors did not increase miR-122-5p and had a weakened capacity to reduce Wnt1. In addition, a key mediator of melanoma survival signaling, the peroxisome proliferator-activated receptor gamma coactivator 1-a (PPARGC1A/PGC1), was involved in miR-122-5p transcription. In conclusion, this study highlights the powerful role miRNAs have in fine-tuning specific G protein–coupled receptor-mediated signaling events by altering the transcription of signaling transduction pathway components. This study also identifies that LPAR3 increases miR-122-5p expression, which occurs mechanistically through the SH3 domain and helps explain why miR-122-5p increases are detected in cancer patient serum. Implications: LPAR3 is partially responsible for the production and secretion of miR-122-5p, found in the serum of a wide variety of patients with cancer.-
dc.languageeng-
dc.relation.ispartofMolecular Cancer Research-
dc.titleMiR-122-5p expression and secretion in melanoma cells is amplified by the LPAR3 SH3–binding domain to regulate WNT1-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1541-7786.MCR-18-0460-
dc.identifier.pmid30266753-
dc.identifier.scopuseid_2-s2.0-85059496128-
dc.identifier.volume17-
dc.identifier.issue1-
dc.identifier.spage299-
dc.identifier.epage309-
dc.identifier.eissn1557-3125-
dc.identifier.isiWOS:000454834200026-

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