pregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanom

Autor(es)

Diogenes Siena, Adamo Davi ^{[1, 2]} ; de Barros, Isabela Ichihara ^{[1, 2]} ; Storti, Camila Baldin ^{[1, 2]} ; Oliveira de Biagi Junior, Carlos Alberto ^{[1, 2]} ; da Costa Carvalho, Larissa Anastacio ^[3] ; Maria-Engler, Silvya Stuchi ^[3] ; Sousa, Josane de Freitas ^[4] ; Silva Jr, Wilson Araujo

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[4] Fed Univ Para UFPA, Inst Biol Sci, Belem, Para - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; v. 26, n. 3, p. 671-683, FEB 2022.
• Citações Web of Science: 1

Resumo

Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis-related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naive and vemurafenib-resistant cell lines and data from a patient before and after resistance, we found that vemurafenib-resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance. (AU)

• Processo FAPESP: 18/04017-9 - Caracterização genômica e funcional de potenciais lncRNAs restritos a melanoma (RMELs)
• Beneficiário: Enilza Maria Espreafico
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/14936-1 - Metabolismo mitocondrial ditando a heterogeneidade e a resistência do melanoma
• Beneficiário: Larissa Anastacio da Costa Carvalho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/04926-6 - Melanoma e quimiorresistência: modelos in vitro e in silico para explorar alvos terapêuticos
• Beneficiário: Silvya Stuchi Maria-Engler
• Modalidade de apoio: Auxílio à Pesquisa - Temático