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CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
Lijun Zhao1, Junying Fan2, Chunyang Zhang3
1Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, 215000, China.
Abstract:
Neuroblastoma (NB) is a common childhood cancer. Circular RNA RAN binding protein 17 (circRANBP17) has been identified to participate in diverse tumor progression. This study aims to explore the function and mechanism of circRANBP17 in NB. The levels of circRANBP17, miR-27b-3p and KDM1A in NB tissues and cells were measured by qRT-PCR. Mouse model assay was performed to investigate the effect of circRANBP17 knockdown on tumor formation in vivo. The levels of circRANBP17 and KDM1A were significantly up-regulated, and the level of miR-27b-3p was strikingly down-regulated in NB tissues and cells (SK-N-SH and SK-N-AS). Functional studies indicated that miR-27b-3p inhibitor mitigated the inhibitory effects on cell proliferation, migration, invasion and the promoting effect on cell apoptosis in SK-N-SH and SK-N-AS cells induced by circRANBP17 knockdown. Also, miR-27b-3p regulated NB cell malignancy by targeting KDM1A. Further studies revealed that miR-27b-3p inhibitor reversed the low expression of KDM1A induced by circRANBP17 knockdown. In support, circRANBP17 knockdown led to inhibition of tumor formation in vivo. In conclusion, circRANBP17 modulated KDM1A to promote cell proliferation, migration, invasion and restrain cell apoptosis in NB by sponging miR-27b-3p, and the new regulatory network may provide a theoretical basis for the further study of NB.
Insights
Circular RNA RAN binding protein 17 (circRANBP17) promotes neuroblastoma (NB) progression by sponging miR-27b-3p and upregulating KDM1A. Knockdown of circRANBP17 inhibits NB tumor formation, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neuroblastoma (NB) is a prevalent pediatric cancer.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in tumor progression.
- circRANBP17 has been implicated in various cancers, but its specific role in NB requires elucidation.
Purpose of the Study:
- To investigate the function and underlying mechanism of circRANBP17 in neuroblastoma.
- To explore the regulatory network involving circRANBP17, miR-27b-3p, and KDM1A in NB.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure expression levels of circRANBP17, miR-27b-3p, and KDM1A.
- In vivo mouse models to assess the impact of circRANBP17 knockdown on tumor formation.
- Functional assays to evaluate cell proliferation, migration, invasion, and apoptosis.
Main Results:
- circRANBP17 and KDM1A were significantly upregulated, while miR-27b-3p was downregulated in NB tissues and cells.
- circRANBP17 knockdown inhibited NB cell proliferation, migration, and invasion, and promoted apoptosis.
- miR-27b-3p targeted KDM1A, and its inhibition reversed the effects of circRANBP17 knockdown on NB cells.
- circRANBP17 knockdown suppressed tumor formation in vivo.
Conclusions:
- circRANBP17 promotes NB progression by sponging miR-27b-3p, leading to KDM1A upregulation.
- This regulatory axis (circRANBP17/miR-27b-3p/KDM1A) plays a critical role in NB cell malignancy.
- The findings provide a potential theoretical basis for novel therapeutic strategies against neuroblastoma.
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