Revisiting the Relationship Between Alzheimer’s Disease and Cancer With a circRNA Perspective

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.

Transcriptomic signatures of Aβ- and tau-induced neuronal dysfunction reveal inflammatory processes at the core of Alzheimer’s disease pathophysiology

“…Previous studies have assessed the usefulness of several of our discovered candidate pharmacological agents targeting affected AD pathways. Converging evidence indicates that cancer treatment may be related to a decreased risk of AD due to a pathophysiological overlap between both diseases, albeit a worsened cognition being in some studies linked to oncology drugs (D. Chen et al, 2021; Frain et al, 2017; Plun-Favreau et al, 2010).…”

CRIT: Identifying RNA-binding protein regulator in circRNA life cycle via non-negative matrix factorization

“…Indeed, we recently found that the expression pattern of circRNA inversely correlated between some cancers and Alzheimer’s disease, suggesting that they may share some common circRNA-mediated mechanisms and pathogenesis. 48 Such analysis would require further fine-tuning of the mining algorithms and obtaining additional mRNA/circRNA expression profiles under specific conditions. Another potential technical extension of CRIT is to apply supervised-learning algorithms to predict circRNA-regulating RBPs based on known or validated regulators.…”

Computational Drug Repurposing Based on a Recommendation System and Drug–Drug Functional Pathway Similarity

“…This is particularly useful in personal drug prescriptions in cancer care and/or combating drug resistance. In addition, accumulated evidence revealed that some cancers share common mechanisms and molecular pathogenesis with neurodegenerative diseases, such as Alzheimer's disease (AD) [64,65]. Thus, this framework can be utilized as a computational tool for generating mechanistic hypotheses and drug replacement for both cancer and AD when the drug activity and multi-omics data are comprehensive.…”