Differentiation of two human neuroblastoma cell lines alters SV2 expression patterns

Abstract

Background The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells

“…Neuroblastoma cell Neuro2a was treated with different compounds along with ATRA for 72 h before measuring the average neurites outgrowth. Considering the differentiation effect of ATRA on neuroblastoma cannot be observed until 5–7 days in multiple studies 20 , 21 , 7 days of ATRA treatment was also added. Several compounds demonstrated a good proliferation-inhibiting activity such as compounds L2 , L5 , L14 , L16 , and L18 ( Supporting Information Fig.…”

“…In the absence of the molecular target of retinoids, combined with the problems of effective blood concentration and considerably more complex crosstalk between oncogenic pathways, it seems difficult to implement differentiation therapy on other malignancies as it did in APL 10 . It takes a longer onset time (ranging from 5 to 28 days) and higher concentration to trigger differentiation in vivo and in vitro compared to APL 20 , 21 , 41 , 42 , 43 , 44 , 45 , 46 . Interestingly, research showed that the activation of the AKT pathway was essential for the differentiation of neuroblastoma induces by retinoids 47 , which causes a conflicting relationship between the widely regarded tumor-promoting mechanism of AKT and the favorable outcome of differentiation therapy in neuroblastoma.…”

Novel DNA methylation-based epigenetic signatures in colorectal cancer from peripheral blood leukocytes

“…The DNAm of cg18144285 in the CpG island within 200 bp upstream of the transcription start site (TSS200) of SV2B displayed the second strongest effect on increased risk for CRC, with strong down-regulation of SV2B in CRC tis-Am J Cancer Res 2024;14(5):2253-2271 sues. Synaptic vesicle glycoprotein 2B (SV2B) is essential to the synaptic machinery in neural and endocrine cells [71,72] and is overexpressed in prostate small-cell neuroendocrine carcinoma [73] and glioblastoma [74]. Of note, our GSEA-GO analysis in CRC detected the ECM-receptor interaction pathways, which play an important role in modulating cancer-cell behaviors [64,65], with SV2B as a key driver; this is consistent with previous findings in gastric cancer [75], which identified SV2B as a strong indicator of ECM-receptor interactions.…”