Abstract
Microtubules (MTs), microfilaments, and intermediate filaments, the main constituents of the cytoskeleton, undergo continuous structural changes (metamorphosis), which are central to cellular growth, division, and release of microvesicles (MVs). Altered MTs dynamics, uncontrolled proliferation, and increased production of MVs are hallmarks of carcinogenesis. Class III beta-tubulin (β3-tubulin), one of seven β-tubulin isotypes, is a primary component of MT, which correlates with enhanced neoplastic cell survival, metastasis and resistance to chemotherapy. We studied the effects of β3-tubulin gene silencing on MTs dynamics, cell cycle, and MVs release in human malignant melanoma cells (A375). The knockdown of β3-tubulin induced G2/M cell cycle arrest, impaired MTs dynamics, and reduced spontaneous MVs release. Additional studies are therefore required to elucidate the pathophysiologic and therapeutic role of β3-tubulin in melanoma.
Highlights
Class III beta-tubulin (β3-tubulin), encoded by the TUBB3 gene, is one of seven beta-tubulin isotypes in the human genome
A375 Cells Express β3-Tubulin mRNA and Protein β3-tubulin is highly expressed in malignant as compared with normal melanocytes, and siRNA knockdown of β3-tubulin hinders the migration of melanoma cells [17]
Using Real-time PCR (RT-PCR) and Western blot analysis, we demonstrated that the A375 human malignant melanoma cells express β3-tubulin mRNA and protein (Figure 1A). siRNA knockdown of β3-tubulin significantly reduced the mRNA and protein expression by 79.3% ± 7.7% (p < 0.001) and 83% ± 4.9% (p < 0.01), respectively
Summary
Class III beta-tubulin (β3-tubulin), encoded by the TUBB3 gene, is one of seven beta-tubulin isotypes in the human genome It is constitutively expressed in neurons of the peripheral and central nervous system, regulating neuronal differentiation and development [1]. Microvesicles (MVs) are secreted by intact cells as microscopic membrane-enclosed sacs ranging in diameter from 100 to 1000 nm. They are formed by plasma membrane protrusions (buds), which close and become separated from the progenitor cell, eventually to be released into the extracellular environment [8,9]. We hypothesize that β3-tubulin interferes with microtubule dynamics, cell cycle regulation, and the spontaneous release of MVs in A375 human malignant melanoma cells
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