Abstract
Cancers evolve from normal tissues and share an endogenous regulatory realm distinctive from that of normal human tissues. Unearthing such an endogenous realm faces challenges due to heterogeneous biology data. This study computes petabyte level data and reveals the endogenous regulatory networks of normal and cancers and then unearths the most important endogenous regulators for normal and cancerous realm. In normal, proteins dominate the entire realm and trans-regulate their targets across chromosomes and ribosomal proteins serve as the most important drivers. However, in cancerous realm, noncoding RNAs dominate the whole realm and pseudogenes work as the most important regulators that cis-regulate their neighbors, in which they primarily regulate their targets within 1 million base pairs but they rarely regulate their cognates with complementary sequences as thought. Therefore, two distinctive mechanisms rule the normal and cancerous realm separately, in which noncoding RNAs endogenously regulate cancers, instead of proteins as currently conceptualized. This establishes a fundamental avenue to understand the basis of cancerous and normal physiology.