Abstract
BackgroundIncreasing evidence indicates an association between the incidence of Alzheimer’s disease (AD) and cancer development. Despite advances being made by comparisons from epidemiological studies, common pathways and molecular mechanisms, little is known about the identities of the circular RNAs (circRNAs) involved in the development and progression of these two pathologies and their possible correlations. The aim of this study was to explore the circRNA relationship between AD and cancer.Materials and MethodsIn this investigation, circRNAs that were significantly dysregulated in AD or associated with AD diagnosis, clinical dementia severity, and neuropathological severity, were examined in a large panel of 28 cancer types. On the basis of shared abnormal circRNAs in AD and cancers, we constructed a circRNA-micro RNA (miRNA)-messenger RNA (mRNA) network by leveraging experimentally identified miRNA-circRNA and miRNA-mRNA interactions from crosslinking-immunoprecipitation sequencing data.ResultsAn inverse correlation of expression pattern was found in acute myeloid leukemia, juvenile myelomonocytic leukemia, renal cell carcinoma, and myelofibrosis. CircRNAs associated with AD diagnosis and clinical severity demonstrated negative correlation in more cancer types. Notably, differentially expressed candidate circRNAs in temporal lobe epilepsy were not associated with any cancers. Gene Ontology and KEGG pathway analysis suggested the circRNA-regulated genes are significantly associated with interleukin-12-mediated signaling and viral response. CircPICALM, circRTN4 and circMAN2A1 are the hub nodes in the circRNA-miRNA-target network.ConclusionOur results indicated the relevance of inflammation signaling as a common pathogenesis shared by cancer and AD and provided novel insight for therapeutics targeting circRNAs.
Highlights
Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects millions of people worldwide (Lane et al, 2018)
CircRNA reads of control tissue and multiple cancer tissues were used for differential expression analysis
For Knight ADRC data, comparing their expression pattern with that in cancer datasets indicated inverse correlations with nine cancer subtypes (Table 1). These correlations were confirmed in acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), renal cell carcinoma (KDNY), and myelofibrosis (MPN) datasets
Summary
Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects millions of people worldwide (Lane et al, 2018). Accumulating evidence suggests a biological link between cancer and AD neuropathology (Snyder et al, 2017) Both are age-associated diseases; one is degenerative and other is over-proliferative, the risks of both increase significantly with age (Childs et al, 2015; Xia et al, 2018). Several epidemiological investigations and meta-analyses suggested a possible inverse relationship between the incidences of these pathologies (Musicco et al, 2013; Zhang et al, 2015) Consistent with this observation, AD is associated with increased cellular death and decreased proliferative signaling, whereas uncontrolled proliferation and apoptosis inhibition are the hallmarks in cancers (Hanahan and Weinberg, 2011; Nudelman et al, 2019). The aim of this study was to explore the circRNA relationship between AD and cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
