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生物钟、衰老及其对癌症的影响。

The circadian clock, aging and its implications in cancer.

机构信息

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

出版信息

Neoplasia. 2023 Jul;41:100904. doi: 10.1016/j.neo.2023.100904. Epub 2023 May 4.

Abstract

Circadian clock orchestrates the intergenic biochemical, physiological and behavioral changes to form an approximate 24h oscillation through the transcription-translation feedback loop (TTFL). Mechanistically, a heterodimer of transcriptional activator formed by BMAL1 and CLOCK, governs the expression of its transcriptional repressors, CRY, PER and REV-ERBα/β proteins, thereby controlling more than 50 % of protein encoding genes in human. There is also increasing evidence showing that tumor microenvironment can disrupt specific clock gene functions to facilitate tumorigenesis. Although there is great progress in understanding the molecular mechanisms of the circadian clock, aging and cancer, elucidating their complex relationships among these processes remains challenging. Herein, the optimization of the chronochemotherapy regimen has not been justified yet for treatment of cancer. Here, we discuss the hypothesis of relocalization of chromatin modifiers (RCM) along with function(s) of the circadian rhythm on aging and carcinogenesis. We will also introduce the function of the chromatin remodeling as a new avenue for rejuvenation of competent tissues to combat aging and cancer.

摘要

生物钟通过转录-翻译反馈环(TTFL)协调基因间的生化、生理和行为变化,形成近似 24 小时的振荡。从机制上讲,由 BMAL1 和 CLOCK 形成的转录激活物二聚体,控制其转录抑制因子 CRY、PER 和 REV-ERBα/β 蛋白的表达,从而控制人类超过 50%的蛋白质编码基因。越来越多的证据表明,肿瘤微环境可以破坏特定的时钟基因功能,从而促进肿瘤发生。尽管人们在理解生物钟、衰老和癌症的分子机制方面取得了很大进展,但阐明这些过程之间的复杂关系仍然具有挑战性。在这里,chronochemotherapy 方案的优化尚未得到证实,以治疗癌症。在这里,我们讨论了染色质修饰物(RCM)沿着生物钟的功能重新定位的假说,以及其在衰老和致癌中的作用。我们还将介绍染色质重塑的功能,作为恢复有能力组织对抗衰老和癌症的新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6a1/10192918/c0434d7001b4/gr1.jpg

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