Beta3-Tubulin is Critical for Microtubule Dynamics, Cell Cycle Regulation, and Spontaneous Release of Microvesicles in Human Malignant Melanoma Cells (A375)

Int J Mol Sci. 2020 Feb 28;21(5):1656. doi: 10.3390/ijms21051656.

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.

Keywords: melanoma; microtubules; microvesicles; β3-tubulin.

MeSH terms

  • Cell Cycle*
  • Cell Line, Tumor
  • Cell-Derived Microparticles / metabolism*
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Microtubules / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Tubulin / genetics
  • Tubulin / metabolism*

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • TUBB3 protein, human
  • Tubulin