Recently, a member of the voltage-dependent potassium channel (Kv) family, the Ether à go-go 1 (Eag1) channel was found to be necessary for cell proliferation, cycle progression and tumorigenesis. However, the therapeutic potential of the Eag1 channel in osteosarcoma remains elusive. In the present study, a recombinant adenovirus harboring shRNA against Eag1 was constructed to silence Eag1 expression in human osteosarcoma MG-63 cells. We observed that Eag1-shRNA inhibited the proliferation and colony formation of MG-63 cells due to the induction of G1 phase arrest. Moreover, in vivo experiments showed that Eag1-shRNA inhibited osteosarcoma growth in a xenograft nude mice model. In addition, selective inhibition of Eag1 significantly decreased the expression levels of cyclin D1 and E. Taken together, our data suggest that the Eag1 channel plays a crucial role in regulating the proliferation and cell cycle of osteosarcoma cells, and represents a new and effective therapeutic target for osteosarcoma.
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http://dx.doi.org/10.3390/ijms15045570 | DOI Listing |
Gene
January 2025
Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address:
The main risk factor for cervical cancer is the persistent infection of high-risk HPV subtypes, notably HPV16. Another contributing factor is proinflammatory prostaglandin E (PGE), a lipid abundantly found in seminal fluid. PGE, along with its receptors (PTGER1-4), contributes to cancer development; however, its specific role in the proliferation of cervical cancer models with high HPV16 copy numbers remains unclear.
View Article and Find Full Text PDFEAG1 depolarization-activated potassium selective channels are important targets for treatment of cancer and neurological disorders. EAG1 channels are formed by a tetrameric subunit assembly with each subunit containing an N-terminal Per-Arnt-Sim (PAS) domain and C-terminal cyclic nucleotide-binding homology (CNBH) domain. The PAS and CNBH domains from adjacent subunits interact and form an intracellular tetrameric ring that regulates the EAG1 channel gating, including the movement of the voltage sensor domain (VSD) from closed to open states.
View Article and Find Full Text PDFBiophys J
July 2024
Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address:
Slow deactivation is a critical property of voltage-gated K channels encoded by the human Ether-à-go-go-Related Gene 1 (hERG). hERG1 channel deactivation is modulated by interactions between intracellular N-terminal Per-Arnt-Sim (PAS) and C-terminal cyclic nucleotide-binding homology (CNBh) domains. The PAS domain is multipartite, comprising a globular domain (gPAS; residues 26-135) and an N-terminal PAS-cap that is further subdivided into an initial unstructured "tip" (residues 1-12) and an amphipathic α-helical region (residues 13-25).
View Article and Find Full Text PDFFront Pharmacol
November 2023
Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, United States.
The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity.
View Article and Find Full Text PDFJ Biol Chem
December 2023
Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, District of Columbia, USA. Electronic address:
Ether-a-go-go (EAG) channels are key regulators of neuronal excitability and tumorigenesis. EAG channels contain an N-terminal Per-Arnt-Sim (PAS) domain that can regulate currents from EAG channels by binding small molecules. The molecular mechanism of this regulation is not clear.
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