MYC dosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer

We hypothesize that dosage compensation of critical genes arises from systems- level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interac- tion network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic pa- rameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overex- press an exogenous MYC, leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpres- sion or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in MYC-amplified colon cancer cells. Finally, we identified negative correlation of MYC dosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneu- ploid cancer progression.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)UCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Salud::Maestría Académica en Bioinformática y Biología de SistemasUCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Ciencias de la Computación e InformáticaUCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Ingeniería EléctricaUCR::Vicerrectoría de Docenci

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Produtividade e teor de sólidos solúveis de frutos de cultivares de morangueiro em ambiente protegido Yield and soluble solids contents of fruits of strawberry cultivars in protected cultivation

O cultivo protegido é uma alternativa para controlar variações climáticas em diferentes locais e épocas de plantio, entretanto, seus efeitos e interações com a cultura do morangueiro ainda são pouco conhecidos. O objetivo desse trabalho foi avaliar a influência de três sistemas de cultivo (túnel alto, túnel baixo e a campo) na produtividade, massa média de frutos e no teor de sólidos solúveis dos frutos das cultivares de morango Dover, Camarosa, Sweet Charlie e Oso Grande em Guarapuava-PR. Quanto à produtividade e massa média de frutos, a cultivar Camarosa foi a melhor nos cultivos em túnel, tanto alto quanto baixo, pelo seu excelente desempenho. Os frutos da cultivar Sweet Charlie apresentaram o maior teor de sólidos solúveis nos três ambientes de cultivo. A produtividade e a massa média dos frutos foram significativamente superiores nos cultivos em túneis, alto e baixo, quando comparados ao cultivo a campo. O ambiente que propiciou maior acúmulo de sólidos solúveis nos frutos foi o túnel alto, diferindo significativamente dos demais ambientes de cultivo.<br>Protected cultivation is an alternative to control the climatic effects in different places and times of planting, however, its effects and interactions with the strawberry crop are little known. The goal of this study was to evaluate the effects of three cropping systems (high tunnel, low tunnel and field) on yield, mean fruit mass and the soluble solids contents of strawberry cultivars Dover, Camarosa, Sweet Charlie and Oso Grande in Guarapuava. Camarosa cultivar presents an excellent performance regarding yield and mean fruit mass in high and low tunnel cultivation; hence, these cropping system can be indicated. Fruits of Sweet Charlie cultivar had the highest content of soluble solids in all the cultivation environments. Yield and mean fruit mass obtained from high and low tunnels were significantly higher than in the field. The environment high tunnel allowed greater accumulation of soluble solids, differing significantly from other evaluated environments