UC.183, UC.110, and UC.84 Ultra-Conserved RNAs Are Mutually Exclusive with miR-221 and Are Engaged in the Cell Cycle Circuitry in Breast Cancer Cell Lines

Genes

Chiara Agnoletto¹  Eva Reali²  Andrea Vecchione³  Marco Galasso⁴  Linda Minotti⁴  Valeria Bertagnolo⁴  Stefano Volinia⁴  Francesca Crudele⁴  Nicoletta Bianchi⁴  Fabio Corrà⁴  Federica Brugnoli⁴  Federica Baldassari⁴  Gianpiero Di Leva⁵ 

[1] Advanced Translational Research Laboratory, Veneto Institute of Oncology IOV-IRCCS, 35127 Padua, Italy;Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy;Department of Medical Surgical Science and Translational Medicine-c/o Azienda Ospedaliera Sant’Andrea, Via di Grottarossa 1035, 00189 Rome, Italy;Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA), Department of Translational Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy;School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Stoke-on-Trent ST4 7QB, UK;

关键词: UCR;    MIR221;    breast cancer;    cell cycle;    capivasertib;    alpelisib;   

DOI  :  10.3390/genes12121978

来源: DOAJ

【 摘 要 】

In the human genome, there are about 600 ultra-conserved regions (UCRs), long DNA sequences extremely conserved in vertebrates. We performed a large-scale study to quantify transcribed UCR (T-UCR) and miRNA levels in over 6000 cancer and normal tissue samples to find possible correlation between these kinds of regulatory molecules. Our analysis evidenced several non-coding RNAs showing negative co-regulation with miRNAs; among them, we focused on miR-221 to investigate any relationship with its pivotal role in the cell cycle. We have chosen breast cancer as model, using two cell lines with different phenotypes to carry out in vitro treatments with siRNAs against T-UCRs. Our results demonstrate that the expression of uc.183, uc.110, and uc.84 T-UCRs is mutually exclusive with miR-221 and is engaged in the regulation of CDKN1B expression. In addition, tests with a set of anticancer drugs, including BYL719, AZD5363, AZD8055, AZD7762, and XL765, revealed the modulation of specific T-UCRs without alteration of miR-221 levels.

【 授权许可】

Unknown