Partner of NOB1 homolog transcriptionally activated by E2F transcription factor 1 promotes the malignant progression and inhibits ferroptosis of pancreatic cancer.
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引用次数: 0
Abstract
Pancreatic cancer (PC) is one of the deadliest malignancies. Partner of NOB1 homolog (PNO1) has been reported to be involved in tumorigenesis. However, the role of PNO1 in PC remains to be elucidated. The purpose of this study was to examine the effects of PNO1 on the progression of PC and the possible mechanism related to E2F transcription factor 1 (E2F1), a transcription factor predicted by the JASPAR database to bind to the PNO1 promoter region and promoted the proliferation of pancreatic ductal adenocarcinoma. First, PNO1 expression in PC tissues and its association with survival rate were analyzed by the Gene Expression Profiling Interactive Analysis database. Western blot and reverse transcription-quantitative polymerase chain reaction were used to evaluate PNO1 expression in several PC cell lines. After PNO1 silencing, cell proliferation, migration, and invasion were measured by colony formation assay, 5-ethynyl-2'-deoxyuridine staining, wound healing, and transwell assays. Then, the lipid reactive oxygen species in PANC-1 cells was estimated by using C11-BODIPY581/591 probe. The levels of glutathione, malondialdehyde, and iron were measured. The binding between PNO1 and E2F1 was confirmed by luciferase and chromatin immunoprecipitation (ChIP) assays. Subsequently, E2F1 was overexpressed in PANC-1 cells with PNO1 knockdown to perform the rescue experiments. Results revealed that PNO1 was highly expressed in PC tissues and PNO1 expression was positively correlated with overall survival rate and disease-free survival rate. Significantly elevated PNO1 expression was also observed in PC cell lines. PNO1 knockdown inhibited the proliferation, migration, and invasion of PANC-1 cells. Moreover, ferroptosis was promoted in PNO1-silenced PANC-1 cells. Results of luciferase and ChIP assays indicated that E2F1 could bind to PNO1 promoter region. Rescue experiments suggested that E2F1 overexpression reversed the impacts of PNO1 depletion on the malignant behaviors and ferroptosis in PANC-1 cells. Summing up, PNO1 transcriptionally activated by E2F1 promotes the malignant progression and inhibits the ferroptosis of PC.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.