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Published on: October 25, 2019
Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These
Eutiquio Gutierrez1,2, Ian Cahatol3,4, Cedric A R Bailey3,5
1College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA. Egutierrez@westernu.edu.
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.
Insights
RhoB, a GTPase, regulates cell functions and its downregulation links to cancer. Restoring RhoB may offer cancer prevention and therapeutic strategies.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- RhoB, a Ras homolog GTPase, is crucial for intracellular signaling pathways.
- Dysregulation of RhoB is linked to tumorigenesis via pathways like EGFR, Ras, and PI3K/Akt.
- RhoB expression is modulated by epigenetic factors including HDACs and microRNAs.
Purpose of the Study:
- To investigate the role of RhoB in cellular regulation and its connection to tumorigenesis.
- To explore the link between age-related decline in RhoB and cancer propensity.
- To assess the potential of RhoB restoration for cancer prevention and therapy.
Main Methods:
- Analysis of RhoB's interaction with key signaling pathways (EGFR, Ras, PI3K/Akt/mTOR, MYC).
- Examination of regulatory mechanisms including HDACs and microRNAs affecting RHOB expression.
- Assessment of RhoB's tissue-specific roles in tumorigenesis.
Main Results:
- RhoB interfaces with critical signaling pathways influencing cell structure and function.
- Downregulation of RhoB is associated with increased tumorigenesis.
- RhoB's functions in vesicle trafficking, cell motility, and cell cycle are vital.
Conclusions:
- RhoB plays a significant role in cellular regulation and its loss contributes to cancer.
- Age-related decline in RhoB may increase cancer risk.
- Restoring RhoB expression presents a potential strategy for cancer prevention and treatment.
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