RESUMO
Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, making it difficult to develop effective therapies. In order to identify novel genes critical to OCCC growth, we carried out a comprehensive CRISPR-Cas9 knockout screen against cell growth using an OCCC cell line and a normal ovarian surface epithelium cell line. We identified the gene encoding DHX38/PRP16, an ATP-dependent RNA helicase involved in splicing, as critical for the growth and tumorigenesis of OCCC. DHX38/PRP16 knockdown in OCCC cells, but not normal cells, induces apoptosis and impairs OCCC tumorigenesis in a mouse model. Our results suggest that DHX38/PRP16 may play a role in OCCC tumorigenesis and could potentially be a promising therapeutic target.
Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Fatores de Processamento de RNA , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Animais , Sistemas CRISPR-Cas/genética , Carcinogênese/genética , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Neoplasias Ovarianas/tratamento farmacológico , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/uso terapêuticoRESUMO
Squaraine dyes have significant potential for use in organic photovoltaic devices because their chemical and packing structure tunability leads to a broad solid state panchromaticity. Nevertheless, broadening of the spectrum does not always give rise to increasing power conversion efficiencies. Furthermore, the same processing strategy used to make devices from different squaraines does not lead to the same optimized performance. In this work, by varying the environmental conditions of a set of anilinic squaraines, we demonstrate that spin-cast thin films are made up of a complex set of states, with each state contributing differently to the overall device efficiency. We demonstrate crystallochromy in that small changes in the packing structure give rise to dramatically different absorption spectra. Through a remarkable comparison between squaraines in poly(methyl methacrylate) solid solution and squaraine:PC60BM blends, we also show long-range and orientational disorder broadening, which distorts the ability to correlate qualitative spectroscopic assessment with an understanding of the device mechanism. We conclude that a full quantitative assessment of the populations of each excited state must be carried out in order to make progress toward an improved understanding of each state's contribution to charge transfer at the bulk heterojunction interface.
