Objective: To probe into the expression of circular RNA circNHSL1 in pediatric neuroblastoma and its role in chemotherapy resistance. Methods: A total of 60 children with neuroblastoma who received surgery combined with doxorubicin and cisplatin chemotherapy in our hospital from 2016 to 2019 were collected

including 35 cases with chemotherapy sensitivity and 25 cases with chemotherapy resistance. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression difference of circNHSL1 in children with neuroblastoma and chemotherapy resistance. Adriamycin-resistant strain of human neuroblastoma cell SH-SY5Y was performed

and the expression of circNHSL1 in the adriamycin-resistant cells was detected. Through circNHSL1-silenced cells

cell proliferation and apoptosis were observed by cell counting kit (CCK-8) and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the possible changes in transforming growth factor-β (TGF-β)/Smad signaling pathway

and human recombinant TGF-β1 was administered for recovery experiment to observe its role in circNHSL1-silenced cells. Results: The expression of circular RNA circNHSL1 in neuroblastoma was higher than that in normal tissues (P<0.01)

and the expression in chemotherapy-resistant children and drug-resistant cell strains was higher than that in chemotherapy-sensitive children (P<0.05). In chemotherapy-resistant cells

the proliferation activity of circNHSL1-silenced cells decreased

while the apoptosis rate increased (P<0.01)

the secretion level and expression of TGF-β1 and its downstream expression of p-Smad2 and p-Smad3 decreased (P<0.01). After treated with human recombinant TGF-β1

the cell proliferation activity increased significantly

while the apoptosis rate decreased

and the drug resistance was restored. Conclusion: Circular RNA circNHSL1 is highly expressed in children with neuroblastoma and chemotherapy resistant tissues

which may participate into the chemotherapy resistance by activating TGF-β/Smad signaling pathway.