1. Regulatory effects of miR-19a on MAD2 expression and tumorigenesis in gastric cancer
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Universidad Autónoma de Madrid, Bargiela-Iparraguirre, Jone, Herrero, Jorge M., Pajuelo-Lozano, Natalia, Pérez, M., Perona Abellón, Rosario, Quiroga, Adoración G., Calés, Carmela, Sánchez-Pérez, Isabel, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Universidad Autónoma de Madrid, Bargiela-Iparraguirre, Jone, Herrero, Jorge M., Pajuelo-Lozano, Natalia, Pérez, M., Perona Abellón, Rosario, Quiroga, Adoración G., Calés, Carmela, and Sánchez-Pérez, Isabel
- Abstract
Gastric cancer (GC) is worldwide the sixth most diagnosed and third leading cause of cancer deaths, with poor and late prognosis, probably due to post-surgery adjuvant treatment resistance and lack of a thorough panel of prognostic markers. We have previously shown that mitotic arrest deficient 2 (MAD2, encoded by MAD2L1), a key protein of the spindle assembly checkpoint, is relevant in GC cells; its interference impairs migration and growth, while its overexpression correlates with tumorigenesis.1 Here we show a similar correlation with overall survival (OS) in a pilot patient series. We hypothesized that MAD2 overexpression might relate to micro-RNA (miRNA) deregulation. Bioinformatic analysis identified miRNAs specifically targeting MAD2L1-3′UTR. Expression of miR-19a and miR-203 inversely correlated with MAD2L1 expression in GC cell lines and patients' samples. A broader analysis using Cancer Genome Atlas data showed that only high miR-19 levels correlated with a better OS, especially in patients overexpressing MAD2L1. In GC cells, miR-19a expression reduced cell migration and invasion capability and increased apoptosis, in combination with classical and new antitumoral drugs. We propose that miR-19a is a critical regulator of MAD2 protein in GC, with potential clinical use as a prognostic biomarker, and as a model for MAD2 interfering agent design with therapeutical potential.
- Published
- 2023