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hsa_circ_0013401 通过海绵吸附 miR-195 释放 PAK2 来加速神经母细胞瘤细胞的生长和转移，阻止其凋亡和自噬。

hsa_circ_0013401 Accelerates the Growth and Metastasis and Prevents Apoptosis and Autophagy of Neuroblastoma Cells by Sponging miR-195 to Release PAK2.

机构信息

Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China.

出版信息

Oxid Med Cell Longev. 2021 Nov 22;2021:9936154. doi: 10.1155/2021/9936154. eCollection 2021.

DOI:10.1155/2021/9936154
PMID:34853631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8629642/
Abstract

BACKGROUND

Increased levels of circRNAs have been identified in a variety of cancers. However, the specific functions and mechanisms of circRNAs in neuroblastoma (NB) have not been fully explored.

METHODS

The levels of hsa_circ_0045997, hsa_circ_0080307, hsa_circ_0013401, hsa_circ_0077578, and microRNA-195 were confirmed by RT-qPCR in NB. Gain- and loss-of-function assays and rescue experiments were conducted to determine the influence of hsa_circ_0013401, miR-195, and P21-activated kinase 2 (PAK2) on the proliferation, apoptosis, autophagy, migration, and invasion of NB cells. Regulatory gene targets were validated by the luciferase assay. A xenograft mouse model was used to determine the effects of hsa_circ_0013401.

RESULTS

hsa_circ_0013401 was highly expressed, miR-195 was lowly expressed, and there was a negative correlation between hsa_circ_0013401 and miR-195 in NB. The inhibitory effects of hsa_circ_0013401 knockdown suppressed the proliferation, migration, and invasion and induced the apoptosis and autophagy of NB cells by targeting miR-195 to downregulate PAK2 expression. Luciferase reporter assays showed that miR-195 was a direct target of hsa_circ_0013401, and was the downstream target gene of miR-195. studies showed that hsa_circ_0013401 promotes tumor formation.

CONCLUSIONS

hsa_circ_0013401 induced NB progression through miR-195 to enhance PAK2. Therefore, we might highlight a novel regulatory axis (hsa_circ_0013401/miR-195/PAK2) in NB.

摘要

背景

circRNAs 在多种癌症中水平升高。然而，circRNAs 在神经母细胞瘤（NB）中的具体功能和机制尚未完全探索。

方法

通过 RT-qPCR 证实 NB 中 hsa_circ_0045997、hsa_circ_0080307、hsa_circ_0013401、hsa_circ_0077578 和 microRNA-195 的水平。通过增益和缺失功能测定以及挽救实验，确定 hsa_circ_0013401、miR-195 和 P21 激活激酶 2（PAK2）对 NB 细胞增殖、凋亡、自噬、迁移和侵袭的影响。通过荧光素酶测定验证调节基因靶标。使用异种移植小鼠模型来确定 hsa_circ_0013401 的作用。

结果

hsa_circ_0013401 高表达，miR-195 低表达，NB 中 hsa_circ_0013401 和 miR-195 呈负相关。通过靶向 miR-195 下调 PAK2 表达抑制 hsa_circ_0013401 敲低对 NB 细胞增殖、迁移和侵袭的抑制作用，并诱导细胞凋亡和自噬。荧光素酶报告测定表明，miR-195 是 hsa_circ_0013401 的直接靶标，并且是 miR-195 的下游靶基因。体内研究表明，hsa_circ_0013401 促进肿瘤形成。

结论

hsa_circ_0013401 通过 miR-195 增强 PAK2 诱导 NB 进展。因此，我们可能在 NB 中强调了一个新的调节轴（hsa_circ_0013401/miR-195/PAK2）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0e2/8629642/3d37348736c9/OMCL2021-9936154.011.jpg
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