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长链非编码 RNA 通过海绵吸附作用抑制脑源性神经营养因子/细胞外信号调节激酶通路抑制神经胶质瘤细胞的增殖和迁移。

lncRNA sponges and inhibits BDNF/ERK pathway to suppress glioma cell proliferation and migration.

机构信息

Department of Neurosurgery, Huabei Petroleum Administration Bureau General Hospital, Shijiazhuang, Hebei, China.

Department of Neurosurgery, The Second Hospital of Hebei Medical University, Renqiu, Hebei, China.

出版信息

Aging (Albany NY). 2023 Apr 14;15(8):3021-3034. doi: 10.18632/aging.204655.

DOI:10.18632/aging.204655
PMID:37100464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10188346/
Abstract

OBJECTIVE

Gliomas as primary cerebral malignancies frequently occurring in adults have relatively high morbidity and mortality. The underlying role of long non-coding ribonucleic acids (lncRNAs) in malignancies has attracted much attention, among which tumor suppressor candidate 7 () is a novel tumor suppressor gene whose regulatory mechanism in human cerebral gliomas remains inconclusive.

METHODS AND RESULTS

In this study, bioinformatics analysis indicated that could specifically bind to microRNA (miR)-10a-5p, and according to quantitative polymerase chain reaction (q-PCR), was up-regulated in human glioma cells and negatively correlated with expression. Dual-luciferase reporter gene assay showed the ability of to bind to , and overexpression of notably inhibited expression, restrained human glioma cell proliferation and migration, and regulated cell cycle and cyclin expression via the brain-derived neurotrophic factor/extracellular signal-regulated kinase (BDNF/ERK) pathway. The inhibitory effect of on was also verified by designing overexpression and knockdown panels for wound healing, Transwell and Western blotting assays.

CONCLUSIONS

suppresses human glioma cell proliferation and migration by negatively modulating and inhibiting the BDNF/ERK pathway, thus acting as a tumor suppressor gene in human gliomas.

摘要

目的

作为成人中常见的原发性脑恶性肿瘤,神经胶质瘤的发病率和死亡率相对较高。长链非编码核糖核酸(lncRNA)在恶性肿瘤中的潜在作用引起了广泛关注,其中肿瘤抑制候选基因 7()是一种新型的肿瘤抑制基因,其在人类脑胶质瘤中的调控机制尚不清楚。

方法和结果

在这项研究中,生物信息学分析表明可以特异性结合 microRNA(miR)-10a-5p,根据实时定量聚合酶链反应(q-PCR)结果,在人神经胶质瘤细胞中上调,且与表达呈负相关。双荧光素酶报告基因检测显示了与的结合能力,过表达明显抑制了的表达,通过脑源性神经营养因子/细胞外信号调节激酶(BDNF/ERK)通路抑制人神经胶质瘤细胞的增殖和迁移,并调节细胞周期和周期蛋白的表达。通过设计过表达和敲低载体进行划痕愈合、Transwell 和 Western blot 实验,进一步验证了对的抑制作用。

结论

通过负调控和抑制 BDNF/ERK 通路,抑制人神经胶质瘤细胞的增殖和迁移,从而在人神经胶质瘤中作为肿瘤抑制基因发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/1e2f20308708/aging-15-204655-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/194b4c0459a2/aging-15-204655-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/7518662e5208/aging-15-204655-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/3f863d7ef9c0/aging-15-204655-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/281f15aeb717/aging-15-204655-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/a4ee11be582d/aging-15-204655-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/0eff5a75789a/aging-15-204655-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/ddcec2fd64b1/aging-15-204655-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/4b37b110c92b/aging-15-204655-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/64becc40218b/aging-15-204655-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/1e2f20308708/aging-15-204655-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/194b4c0459a2/aging-15-204655-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/7518662e5208/aging-15-204655-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/3f863d7ef9c0/aging-15-204655-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/281f15aeb717/aging-15-204655-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/a4ee11be582d/aging-15-204655-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/0eff5a75789a/aging-15-204655-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/ddcec2fd64b1/aging-15-204655-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/4b37b110c92b/aging-15-204655-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/64becc40218b/aging-15-204655-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89bf/10188346/1e2f20308708/aging-15-204655-g010.jpg

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