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Noncoding RNAs endogenously rule the cancerous regulatory realm while proteins govern the normal.

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.

SUBMITTER: Wang A

PROVIDER: S-EPMC9062140 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Noncoding RNAs endogenously rule the cancerous regulatory realm while proteins govern the normal.

Wang Anyou A

Computational and structural biotechnology journal 20220420

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 <i>trans</i>-regulate their targets acr ...[more]

PMID: 35521545

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Project description:BackgroundMicroglia have been implicated in the pathogenesis of radiation-induced brain injury (RIBI), which severely influences the quality of life during long-term survival. Recently, irradiated microglia were speculated to present an aging-like phenotype. Long noncoding RNAs (lncRNAs) have been recognized to regulate a wide spectrum of biological processes, including senescence; however, their potential role in irradiated microglia remains largely uncharacterized.MethodsWe used bioinformatics and experimental methods to identify and analyze the senescence phenotype of irradiated microglia. Western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and quantitative real-time reverse transcription-polymerase chain reaction were performed to clarify the relationship between the radiation-induced differentially expressed lncRNAs (RILs) and the distinctive molecular features of senescence in irradiated microglia.ResultsWe found that the senescence of microglia could be induced using ionizing radiation (IR). A mutual regulation mode existed between RILs and three main features of the senescence phenotype in irradiated microglia: inflammation, the DNA damage response (DDR), and metabolism. Specifically, for inflammation, the expression of two selected RILs (ENSMUST00000190863 and ENSMUST00000130679) was dependent on the major inflammatory signaling pathways of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). The two RILs modulated the activation of NF-κB/MAPK signaling and subsequent inflammatory cytokine secretion. For the DDR, differential severity of DNA damage altered the expression profiles of RILs. The selected RIL, ENSMUST00000130679, promoted the DDR. For metabolism, blockade of sterol regulatory element-binding protein-mediated lipogenesis attenuated the fold-change of several RILs induced by IR.ConclusionsOur findings revealed that certain RILs interacted with senescence in irradiated microglia. RILs actively participated in the regulation of senescence features, suggesting that RILs could be promising intervention targets to treat RIBI.

Dataset Information

Noncoding RNAs endogenously rule the cancerous regulatory realm while proteins govern the normal.

Publications

Noncoding RNAs endogenously rule the cancerous regulatory realm while proteins govern the normal.

Similar Datasets

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