Browsing by Subject "Cdc42"

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    Circular RNA circ_SKA3 enhances gastric cancer development by targeting miR-520h
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Chuntao; Jiang, Hao; Peng, Jiaqun; Weng, Duanshun; Zhang, Yu; Zhou, Yanxun; Zhang, Qin
    Purpose. To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood. Methods. Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)- 520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]- 2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2’- Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively. Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo. Results. Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h. Furthermore, CDC42 was a functional target of miR520h in regulating GC cell behaviors. Conclusion. Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.
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    Roles of Rho small GTPases in the tangentially migrating neurons
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Ito, Hidenori; Morishita, Rika; Tabata, Hidenori; Nagata, Koh-ichi
    Rho small GTPases are members of the Ras superfamily of monomeric 20~30 kDa GTP-binding proteins. These proteins function as molecular switches that regulate various cellular processes such as migration, adhesion and proliferation. Cycling between GDP-bound inactive and GTP-bound active forms is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and GDPdissociation inhibitors (GDIs). Among 20 different mammalian Rho GTPases identified to date, RhoA, Rac1 and Cdc42 have been most extensively investigated; regulation of migration, adhesion and proliferation by these proteins have been well documented in a variety of cell types, including neurons. In neurons, RhoA, Rac1 and Cdc42 are crucial for axon guidance, dendrite formation and spine morphogenesis, where molecular machineries required for cell migration and adhesion play essential roles. Recently, accumulating experimental data indicate the participation of Rho GTPases in neuronal cell migration. To establish the cortical lamination and synapse network formation, highly specialized modes of neuron migration are essential, which include 1) radial migration of excitatory pyramidal neurons along radial glial fibers, 2) tangential migration of GABAergic cortical (inhibitory) interneurons along emerging axon tracts and 3) chain migration of interneurons ensheathed in a glial network, which is observed only in olfactory bulb-directed adult neurogenesis. While roles of Rho GTPases in the radial migration have been well reviewed, knowledge of their functions in tangential migration and chain migration are fragmentary to date. In this review, we focus on the roles of Rho small GTPases and their related molecules in tangential migration, together with the possible application of the electroporation method to analyses for this mode of migration in embryonic and postnatal mouse brain.