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PODNL1通过调节Akt/mTOR通路促进胶质瘤细胞的增殖和迁移。

PODNL1 promotes cell proliferation and migration in glioma via regulating Akt/mTOR pathway.

作者信息

Geng Yibo, Zuo Pengcheng, Li Xiao-Ou, Zhang Liwei

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

China National Clinical Research Center for Neurological Disease, Nan Si Huan Xi Lu 119, Fengtai District, Beijing 100070, China.

出版信息

J Cancer. 2020 Aug 27;11(21):6234-6242. doi: 10.7150/jca.46901. eCollection 2020.

Abstract

Emerging studies have determined that the small leucine-rich proteoglycan (SLRP) family can aggravate tumor progression. However, the biological function of podocan-like protein 1 (PODNL1), a novel member of the SLRP family, has not been investigated. Therefore, our study focused on the function and regulatory mechanism of PODNL1 in glioma. Both the Gene Expression Profiling Interactive Analysis (GEPIA) and the Chinese Glioma Genome Atlas (CGGA) database were used to analyze the expression level and survival risk of PODNL1 in glioma. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to detect the mRNA and protein expression, respectively. Celltiter-Glo and colony formation assays were used to evaluate cell proliferation. Migration capacity was measured by Transwell and wound healing assays. Flow cytometry was utilized to assess the apoptotic rate. The expression of PODNL1 predicted the poor prognosis in glioma patients. Silencing of PODNL1 inhibited cell proliferation, migration, and induced epithelial-like phenotype. In addition, knockdown of PODNL1 also induced cell apoptosis. Moreover, the cell growth and migration inhibited by PODNL1 knockdown could be partially rescued with Akt activator. Conversely, PODNL1 overexpression promoted cell growth and migration, which were suppressed by Akt inhibitor. PODNL1, a promising predictive indicator of poor prognosis, resulted in greater proliferation, migration and epithelial-mesenchymal transition (EMT) process. Moreover, PODNL1 promoted aggressive glioma behavior by activating Akt/mTOR pathway, providing a novel therapeutic target for glioma.

摘要

新兴研究已确定富含亮氨酸的小分子蛋白聚糖(SLRP)家族可加剧肿瘤进展。然而,SLRP家族的新成员足突蛋白样蛋白1(PODNL1)的生物学功能尚未得到研究。因此,我们的研究聚焦于PODNL1在胶质瘤中的功能及调控机制。利用基因表达谱交互分析(GEPIA)和中国胶质瘤基因组图谱(CGGA)数据库分析PODNL1在胶质瘤中的表达水平及生存风险。分别应用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法检测mRNA和蛋白质表达。采用Celltiter-Glo和集落形成实验评估细胞增殖。通过Transwell实验和划痕愈合实验检测迁移能力。利用流式细胞术评估凋亡率。PODNL1的表达预示着胶质瘤患者预后不良。沉默PODNL1可抑制细胞增殖、迁移,并诱导上皮样表型。此外,敲低PODNL1还可诱导细胞凋亡。而且,PODNL1敲低所抑制的细胞生长和迁移可被Akt激活剂部分挽救。相反,PODNL1过表达促进细胞生长和迁移,而这被Akt抑制剂所抑制。PODNL1是一种预后不良的有前景的预测指标,可导致更强的增殖、迁移及上皮-间质转化(EMT)过程。此外,PODNL1通过激活Akt/mTOR通路促进胶质瘤的侵袭行为,为胶质瘤提供了一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acdb/7532506/f92316e3af8e/jcav11p6234g001.jpg

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