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肿瘤发生和衰老过程中RhoB基因表达的调控及其在这些过程中的潜在应用。

Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These Processes.

作者信息

Gutierrez Eutiquio, Cahatol Ian, Bailey Cedric A R, Lafargue Audrey, Zhang Naming, Song Ying, Tian Hongwei, Zhang Yizhi, Chan Ryan, Gu Kevin, Zhang Angel C C, Tang James, Liu Chunshui, Connis Nick, Dennis Phillip, Zhang Chunyu

机构信息

College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA.

Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90509, USA.

出版信息

Cancers (Basel). 2019 Jun 13;11(6):818. doi: 10.3390/cancers11060818.

Abstract

RhoB, a member of the Ras homolog gene family and GTPase, regulates intracellular signaling pathways by interfacing with epidermal growth factor receptor (EGFR), Ras, and phosphatidylinositol 3-kinase (PI3K)/Akt to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. Functionally, RhoB, part of the Rho GTPase family, regulates intracellular signaling pathways by interfacing with EGFR, RAS, and PI3K/Akt/mammalian target of rapamycin (mTOR), and MYC pathways to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. RHOB expression has a complex regulatory backdrop consisting of multiple histone deacetyltransferase (HDACs 1 and 6) and microRNA (miR-19a, -21, and -223)-mediated mechanisms of modifying expression. The interwoven nature of RhoB's regulatory impact and cellular roles in regulating intracellular vesicle trafficking, cell motion, and the cell cycle lays the foundation for analyzing the link between loss of RhoB and tumorigenesis within the context of age-related decline in RhoB. RhoB appears to play a tissue-specific role in tumorigenesis, as such, uncovering and appreciating the potential for restoration of RHOB expression as a mechanism for cancer prevention or therapeutics serves as a practical application. An in-depth assessment of RhoB will serve as a springboard for investigating and characterizing this key component of numerous intracellular messaging and regulatory pathways that may hold the connection between aging and tumorigenesis.

摘要

RhoB是Ras同源基因家族和GTP酶的成员之一,它通过与表皮生长因子受体(EGFR)、Ras以及磷脂酰肌醇3激酶(PI3K)/Akt相互作用来调节细胞内信号通路,从而调控细胞结构和功能的反应。值得注意的是,EGFR、Ras和PI3K/Akt通路可导致RhoB下调,同时与肿瘤发生倾向增加相关。在功能上,作为Rho GTP酶家族一部分的RhoB,通过与EGFR、RAS、PI3K/Akt/雷帕霉素哺乳动物靶蛋白(mTOR)以及MYC通路相互作用来调节细胞内信号通路,进而调控细胞结构和功能的反应。值得注意的是,EGFR、Ras和PI3K/Akt通路可导致RhoB下调,同时与肿瘤发生倾向增加相关。RHOB的表达具有复杂的调控背景,由多种组蛋白去乙酰化酶(HDACs 1和6)以及微小RNA(miR - 19a、- 21和- 223)介导的表达修饰机制组成。RhoB在调节细胞内囊泡运输、细胞运动和细胞周期方面的调控作用与细胞功能之间相互交织的性质,为在RhoB随年龄下降的背景下分析RhoB缺失与肿瘤发生之间的联系奠定了基础。RhoB似乎在肿瘤发生中发挥着组织特异性作用,因此,揭示并认识到恢复RHOB表达作为癌症预防或治疗机制的潜力具有实际应用价值。对RhoB的深入评估将成为研究和表征众多细胞内信号传递和调控通路这一关键组成部分的跳板,而这些通路可能与衰老和肿瘤发生之间存在联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a469/6627600/248c4f6b8873/cancers-11-00818-g001.jpg

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