Abstract:
All cancers share an endogenous regulatory realm. Understanding this regulatory realm helps to comprehend the universal mechanism of all cancers; however, the conventional approach fails to uncover it due to heterogeneous biological data. This study reveals the endogenous regulatory network of all cancers by identifying endogenous regulatory interactions from big heterogeneous RNA_seq data and unearths the most important endogenous regulators for the cancerous realm. Noncoding RNAs predominate the entire cancerous realm and pseudogenes serve as the most important mediators cis-regulating their neighbors, in which they primarily mediate their targets within 1 million base pairs but they rarely target their cognates with complementary sequences as thought. Clinical data also validate noncoding RNAs as the deadliest universal regulators for all cancers. Furthermore, noncoding RNA biomarkers can discriminate all cancer types from normal tissues with high accuracy. Therefore, noncoding RNAs, instead of proteins, as traditionally thought, function as endogenous rulers that crucially rule the regulatory realm of all cancers.
