SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR-410 in human neuroblastoma cells

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in children and despite aggressive therapy survival rates remain low. One of the contributing factors for low survival rates is aggressive tumor angiogenesis, which is known to increase due to radiation, one of the standard therapies for neuroblastoma. Therefore, targeting tumor angiogenesis can be a viable add-on therapy for the treatment of neuroblastomas. In the present study, we demonstrate that overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses radiation induced angiogenesis in SK-N-BE(2) and NB1691 neuroblastoma cells. We observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF-A targeting microRNA. SPARC overexpression alone or in combination with miR-410 and radiation was shown to be effective at reducing angiogenesis. Moreover, addition of miR-410 inhibitors reversed SPARC mediated inhibition of VEGF-A in NB1691 cells but not in SK-N-BE(2) NB cells. In conclusion, the present study demonstrates that the over-expression of SPARC in combination with radiation reduced tumor angiogenesis by downregulating VEGF-A via miR-410.

LncRNA OIP5-AS1 loss-induced microRNA-410 accumulation regulates cell proliferation and apoptosis by targeting KLF10 via activating PTEN/PI3K/AKT pathway in multiple myeloma

“…MiR-410, a novel cancer-related microRNA, has been found to be dysregulated in cancers. 13 , 14 , 15 Li et al demonstrated that miR-410 promotes cell proliferation by targeting BRD7 in non-small cell lung cancer (NSCLC). 16 In prostate cancer, miR-410 could be served as a potential serum biomarker for the diagnosis.…”

Glucose affects cell viability, migration, angiogenesis and cellular adhesion of human retinal capillary endothelial cells via SPARC

“…In gastric cancer, Zhang et al (30) demonstrated that the suppression of angiogenesis by SPARC may be mediated by downregulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-7). Notably, overexpression of SPARC has also been demonstrated to be involved in radiation-reduced tumor angiogenesis by downregulating VEGF-A via microRNA-410 (31). The pathway that is associated with angiogenesis in retinopathy and is regulated by SPARC remains unclear.…”

Vascular-Derived SPARC and SerpinE1 Regulate Interneuron Tangential Migration and Accelerate Functional Maturation of Human Stem Cell-Derived Interneurons

“…We found that both proteins significantly increased the rate and overall number of interneurons that migrated into the cortex over time ( Figure 3G). SPARC and SerpinE1 have been shown to inhibit both endothelial cell migration and proliferation (Boyineni et al, 2016;Hasselaar and Sage, 1992;Lane et al, 1994;Menashi et al, 1993).…”