Potential therapies targeting nuclear metabolic regulation in cancer

作者全名："Chen, Yanjie; Xu, Jie; Liu, Xiaoyi; Guo, Linlin; Yi, Ping; Cheng, Chunming"

作者地址："[Chen, Yanjie; Xu, Jie; Liu, Xiaoyi; Yi, Ping] Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China; [Guo, Linlin] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA; [Cheng, Chunming] Ohio State Univ, James Comprehens Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA; [Cheng, Chunming] Ohio State Univ, Coll Med, Columbus, OH 43210 USA"

通信作者："Yi, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China.; Cheng, CM (通讯作者)，Ohio State Univ, James Comprehens Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA.; Cheng, CM (通讯作者)，Ohio State Univ, Coll Med, Columbus, OH 43210 USA."

来源：MEDCOMM

ESI学科分类：　

WOS号：WOS:001109867900001

JCR分区：Q1

影响因子：9.9

年份：2023

卷号：4

期号：6

开始页：　

结束页：　

文献类型：Review

关键词：cancer therapy; DNA methylation; histone modifications; nuclear metabolic enzymes; nuclear metabolic signaling; tumor metabolism

摘要："The interplay between genetic alterations and metabolic dysregulation is increasingly recognized as a pivotal axis in cancer pathogenesis. Both elements are mutually reinforcing, thereby expediting the ontogeny and progression of malignant neoplasms. Intriguingly, recent findings have highlighted the translocation of metabolites and metabolic enzymes from the cytoplasm into the nuclear compartment, where they appear to be intimately associated with tumor cell proliferation. Despite these advancements, significant gaps persist in our understanding of their specific roles within the nuclear milieu, their modulatory effects on gene transcription and cellular proliferation, and the intricacies of their coordination with the genomic landscape. In this comprehensive review, we endeavor to elucidate the regulatory landscape of metabolic signaling within the nuclear domain, namely nuclear metabolic signaling involving metabolites and metabolic enzymes. We explore the roles and molecular mechanisms through which metabolic flux and enzymatic activity impact critical nuclear processes, including epigenetic modulation, DNA damage repair, and gene expression regulation. In conclusion, we underscore the paramount significance of nuclear metabolic signaling in cancer biology and enumerate potential therapeutic targets, associated pharmacological interventions, and implications for clinical applications. Importantly, these emergent findings not only augment our conceptual understanding of tumoral metabolism but also herald the potential for innovative therapeutic paradigms targeting the metabolism-genome transcriptional axis. 1. Cell metabolism and gene control are significantly integrated and regulated by one another.2. There is a positive feedback loop of metabolism-epigenetics-gene regulation which control cancer progression.3. The discovery of metabolic enzymes and their functions in the nucleus will provide more insights into cancer therapy.#image"

基金机构：CQMU Program for Youth Innovation in Future Medicine; NSFC [82072886]; Natural Science Foundation of ChongqingChina [cstc2020jcyj-msxmX0344]; Science and Technology Innovation Project

基金资助正文："The figure is created by the authors and some components in the figure are from the ""Servier Medical Art"" (). This research was funded by an NSFC grant (No. 82072886), Natural Science Foundation of ChongqingChina (No. cstc2020jcyj-msxmX0344), CQMU Program for Youth Innovation in Future Medicine, and the Science and Technology Innovation Project (2020) of Yubei District, Chongqing to Dr. Ping Yi and Pelotonia Postdoc Fellowship and an OSU Department of Radiation-Oncology Basic Research seed Grant to Dr. Chunming Cheng."