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

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

doi:10.3390/cancers11060818

Cancers (Jun 2019)

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

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

Affiliations

Eutiquio Gutierrez: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA
Ian Cahatol: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA
Cedric A.R. Bailey: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA
Audrey Lafargue: Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD 21231, USA
Naming Zhang: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Ying Song: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Hongwei Tian: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Yizhi Zhang: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Ryan Chan: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Kevin Gu: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Angel C.C. Zhang: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
James Tang: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
Chunshui Liu: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
Nick Connis: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Phillip Dennis: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA
Chunyu Zhang: Department of Oncology, The Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA

DOI: https://doi.org/10.3390/cancers11060818
Journal volume & issue: Vol. 11, no. 6
p. 818

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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