The impact of HER2 overexpression on the miRNA and circRNA transcriptomes in two breast cell lines and their vesicles

Author(s)

de Amorim, Maria Galli ^{[1, 2]} ; Branco, Gabriela ^{[1, 2]} ; Valieris, Renan ^[3] ; Tarcitano, Emilio ^{[1, 2]} ; da Silva, Israel Tojal ^[3] ; de Araujo, Luiza Ferreira ^[1] ; Nunes, Diana Noronha ^[1] ; Dias-Neto, Emmanuel ^{[1, 4]}

Affiliation

^[1] AC Camargo Canc Ctr, Lab Med Genom, Sao Paulo, SP - Brazil

^[2] Fundacao Antonio Prudente, Curso Posgrad Oncol, Sao Paulo, SP - Brazil

^[3] AC Camargo Canc Ctr, Lab Computat Biol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Lab Neurociencias Alzira Denise Hertzog Silva LIM, Inst Psiquiatria, Fac Med, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PHARMACOGENOMICS; v. 20, n. 7, p. 493-502, MAY 2019.
• Web of Science Citations: 0

Abstract

HER2 upregulation is related with poor outcome in many tumor types. Whereas anti-HER2 treatment is the standard approach as adjuvant therapy in HER2-overexpressing breast cancer, the frequent relapses reinforce the need for alternative treatments. Here we used next-generation sequencing (NGS)to evaluate miRNAs and circRNAs in the cell-lines HB4a and C5.2, where the latter is a HER2-overexpressing clone of the former, and also from two different populations of their secreted extracellular vesicles. Whereas circRNA-levels were stable, we found at least 16 miRNAs apparently modulated by HER2-expression. The miR223-3p, miR-421 and miR-21-5p were validated in an independent cohort of 431 breast cancer patients from The Cancer Genome Atlas (TCGA). The consistent modulation of these molecules and their possible involvement in the HER2-axis makes them promising new targets to overcome HER2-activation. (AU)

• FAPESP's process: 14/26897-0 - Epidemiology and genomics of gastric adenocarcinomas in Brazil
• Grantee: Emmanuel Dias-Neto
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 17/20278-4 - Detection of drug resistance markers in small cell lung carcinoma
• Grantee: Luíza Ferreira de Araújo
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/04399-0 - Discovery and validation of small RNAs predictive of aggressiveness in breast cancer
• Grantee: Gabriela Pereira Branco
• Support type: Scholarships in Brazil - Master