Wang Anyou
The Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA 92521, USA.
Comput Struct Biotechnol J. 2022 Apr 20;20:1935-1945. doi: 10.1016/j.csbj.2022.04.015. eCollection 2022.
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 -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 -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.
癌症由正常组织演变而来，具有与正常人体组织不同的内源性调控领域。由于生物学数据的异质性，挖掘这样一个内源性领域面临挑战。本研究计算了PB级数据，揭示了正常组织和癌症的内源性调控网络，进而挖掘出正常和癌症领域最重要的内源性调节因子。在正常情况下，蛋白质主导整个领域并跨染色体调控其靶标，核糖体蛋白是最重要的驱动因素。然而，在癌症领域，非编码RNA主导整个领域，假基因作为最重要的调节因子调控其邻近基因，它们主要在100万个碱基对内调控靶标，但很少像人们认为的那样通过互补序列调控其同源基因。因此，两种不同的机制分别统治着正常和癌症领域，其中非编码RNA以内源性方式调控癌症，而非如目前概念所认为的由蛋白质调控。这为理解癌症和正常生理学基础建立了一条基本途径。
