miR96-and miR182-driven regulation of cytoskeleton results in inhibition of glioblastoma motility

Glioblastoma multiforme (GBM) is one of the most common forms of brain tumor. As an excessively invasive tumor type, GBM cannot be fully cured due to its invasion ability into healthy brain tissues. Therefore, molecular mechanisms behind GBM migration and invasion need to be deeply investigated for the development of effective GBM treatments. Cellular motility and invasion are strictly associated with the cytoskeleton, especially with actins and tubulins. Palladin, an actin-binding protein, tightly bundles actins during initial invadopodia and contraction fiber formations, which are essential for cellular motility. Spastin, a microtubule-binding protein, cuts microtubules into small pieces and acts on invadopodia elongation and cellular trafficking of invadopodia-associated proteins. Regulation of proteins such as spastin and palladin involved in dynamic reorganization of the cytoskeleton, are rapidly carried out by microRNAs at the posttranscriptional level. Therefore, determining possible regulatory miRNAs of spastin and palladin is critical to elucidate GBM motility. miR96 and miR182 down-regulate SPAST and PALLD at both transcript and protein levels. Over-expression of miR96 and miR182 resulted in inhibition of the motility. However, over-expression of spastin and palladin induced the motility. Spastin and palladin rescue of miR96- or miR182-transfected U251 MG cells resulted in diminished effects of the miRNAs and rescued the motility. Our results demonstrate that miR96 and miR182 over-expressions inhibit GBM motility by regulating cytoskeleton through spastin and palladin. These findings suggest that miR96 and miR182 should be investigated in more detail for their potential use in GBM therapy.

Automated summary

Glioblastoma multiforme (GBM) is a common brain tumor that cannot be fully cured due to its invasive nature. Investigating the molecular mechanisms of GBM migration and invasion is crucial for developing effective treatments. Cell motility and invasion are closely related to the cytoskeleton, particularly actins and tubulins. Proteins like palladin and spastin play important roles in cellular motility by regulating actin and microtubule dynamics. MicroRNAs, such as miR96 and miR182, can regulate the expression of spastin and palladin, thus affecting GBM motility. Over-expression of miR96 and miR182 inhibits GBM motility, while over-expression of spastin and palladin promotes it. Rescuing the effects of miR96 and miR182 by restoring spastin and palladin expression leads to restored motility. These findings suggest that miR96 and miR182 have potential therapeutic use in GBM treatment.