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微小RNA-1271-5p通过调控ACY-1促进神经母细胞瘤细胞的生长和迁移。

MiR-1271-5p promotes the growth and migration of neuroblastoma cells by regulating ACY-1.

作者信息

Sun Jun, Zhang Xiaowen, Chen Zimin, Ye Xiaoshuo, Zhang Chen

机构信息

Division II of General Surgery, Department of Pediatric Surgery, Shenzhen Children's Hospital, Shenzhen, China.

出版信息

Transl Cancer Res. 2024 Jul 31;13(7):3397-3406. doi: 10.21037/tcr-24-25. Epub 2024 Jul 16.

Abstract

BACKGROUND

Aminoacylase 1 (ACY-1) has been found to be a tumor suppressor gene in neuroblastoma (NB). This study aimed to identify and verify the microRNAs (miRNAs) that may regulate ACY-1 through database prediction analysis, and verify the mutual regulatory effect of miRNA and ACY-1 in NB through cell experiments.

METHODS

The miRNAs that might bind ACY-1 were predicted and selected by TargetScan, miRTarBase and four other databases, the expression of the predicted miRNAs and ACY-1 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in four groups of clinical samples, and the differentially expressed miRNAs were screened. Then, luciferase vector was constructed according to the gene sequence to detect whether ACY-1 binds to the selected miRNA. Then, miR-1271-5p expression was silenced to detect miR-1271-5p function in the growth and migration of NB. Finally, ACY-1 and miR-1271-5p were silenced to change ACY-1 expression, and ACY-1 function in NB and the regulatory role of miR-1271-5p were explored.

RESULTS

ACY-1 was downregulated in NB, miR-1271-5p was upregulated in NB, and miR-1271-5p could be targeted to ACY-1. Silencing miR-1271-5p expression can reduce cell viability and inhibit tumor progression. After interfering with ACY-1 expression in cells, cell viability was enhanced, apoptosis was significantly decreased, and migration and invasion were enhanced. After partially restoring ACY-1 expression, the effect of si-ACY-1 on cells was weakened. In SK-N-SH and SH-SY-5Y cells, the miR-1271-5p inhibitor restored ACY-1 expression and improved ACY-1 function.

CONCLUSIONS

MiR-1271-5p can promote the growth and migration of tumor cells by inhibiting ACY-1 expression in NB.

摘要

背景

已发现氨基酰化酶1(ACY-1)是神经母细胞瘤(NB)中的一种肿瘤抑制基因。本研究旨在通过数据库预测分析鉴定并验证可能调控ACY-1的微小RNA(miRNA),并通过细胞实验验证miRNA与ACY-1在NB中的相互调控作用。

方法

通过TargetScan、miRTarBase和其他四个数据库预测并筛选可能与ACY-1结合的miRNA,采用逆转录-定量聚合酶链反应(RT-qPCR)检测四组临床样本中预测的miRNA和ACY-1的表达,并筛选差异表达的miRNA。然后,根据基因序列构建荧光素酶载体,检测ACY-1是否与所选miRNA结合。接着,沉默miR-1271-5p表达,检测miR-1271-5p在NB生长和迁移中的功能。最后,沉默ACY-1和miR-1271-5p以改变ACY-1表达,探讨ACY-1在NB中的功能及miR-1271-5p的调控作用。

结果

ACY-1在NB中表达下调,miR-1271-5p在NB中表达上调,且miR-1271-5p可靶向ACY-1。沉默miR-1271-5p表达可降低细胞活力并抑制肿瘤进展。干扰细胞中ACY-1表达后,细胞活力增强,凋亡显著减少,迁移和侵袭能力增强。部分恢复ACY-1表达后,si-ACY-1对细胞的作用减弱。在SK-N-SH和SH-SY-5Y细胞中,miR-1271-5p抑制剂恢复了ACY-1表达并改善了ACY-1功能。

结论

在NB中,miR-1271-5p可通过抑制ACY-1表达促进肿瘤细胞的生长和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e7/11319971/ff2d67f129ef/tcr-13-07-3397-f1.jpg

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