Adipose-derived stem cell-derived extracellular vesicles inhibit neuroblastoma growth by regulating GABBR1 activity through LINC00622-mediated transcription factor AR

脂肪干细胞来源的细胞外囊泡通过 LINC00622 介导的转录因子 AR 调节 GABBR1 活性来抑制神经母细胞瘤生长

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作者:Mengguo Guo, Dongpeng Li, Yawen Feng, Mu Li, Bo Yang

Abstract

Neuroblastoma (NB) is a huge threat to children's health. Adipose-derived stem cells-derived extracellular vesicles (ADSC-Evs) can regulate tumor progression. This study aimed to identify the role of ADSC-Evs in NB. Following ADSC-Ev isolation and identification, PKH26-labeled ADSC-Evs were cocultured with NB cells to observe the internalization of ADSC-Evs. ADSC-Ev effects on NB cell proliferation, invasion, and migration were assessed. The regulatory molecules related to NB development were predicted. The expressions of and relations among LINC00622, transcriptional factor androgen receptor (AR), and gamma-aminobutyric acid B-type receptor 1 (GABRR1) were detected and verified. LINC00622 was inhibited in ADSCs to evaluate ADSC-Ev effects on NB cells. Xenograft tumor experiment in nude mice was further performed to evaluate the effects of ADSC-Evs-carried LINC00622 on NB in vivo. ADSC-Evs inhibited NB cell proliferation, invasion, and migration. ADSC-Evs increased GABBR1 expression in NB cells. ADSC-Evs-carried LINC00622 mediated AR to promote GABBR1 expression. Silencing LINC00622 in ADSCs weakened the inhibition of ADSC-Evs on NB cell malignant behaviors. ADSC-Evs reduced tumor growth in nude mice, which was restored after inhibiting LINC00622 expression in ADSCs. We highlighted that ADSC-Evs carried LINC00622 into NB cells to inhibit transcription factor AR and promote GABBR1 expression, thus inhibiting NB cell growth.

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