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PCLAF 通过 E2F1/PTTG1 轴促进神经母细胞瘤 G1/S 细胞周期进程。

PCLAF promotes neuroblastoma G1/S cell cycle progression via the E2F1/PTTG1 axis.

机构信息

Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.

Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, 200092, China.

出版信息

Cell Death Dis. 2022 Feb 24;13(2):178. doi: 10.1038/s41419-022-04635-w.

Abstract

PCLAF (PCNA clamp-associated factor), also known as PAF15/ KIAA0101, is overexpressed in most human cancers and is a predominant regulator of tumor progression. However, its biological function in neuroblastoma remains unclear. PCLAF is extremely overexpressed in neuroblastoma and is associated with poor prognosis. Through the analysis of various data sets, we found that the high expression of PCLAF is positively correlated with increased stage and high risk of neuroblastoma. Most importantly, knocking down PCLAF could restrict the proliferation of neuroblastoma cells in vitro and in vitro. By analyzing RNA-seq data, we found that the enrichment of cell cycle-related pathway genes was most significant among the differentially expressed downregulated genes after reducing the expression of PCLAF. In addition, PCLAF accelerated the G1/S transition of the neuroblastoma cell cycle by activating the E2F1/PTTG1 signaling pathway. In this study, we reveal the mechanism by which PCLAF facilitates cell cycle progression and recommend that the PCLAF/E2F1/PTTG1 axis is a therapeutic target in neuroblastoma.

摘要

PCLAF(PCNA 衔接因子),也称为 PAF15/ KIAA0101,在大多数人类癌症中过表达,是肿瘤进展的主要调节剂。然而,其在神经母细胞瘤中的生物学功能尚不清楚。PCLAF 在神经母细胞瘤中极度过表达,与预后不良相关。通过对各种数据集的分析,我们发现 PCLAF 的高表达与神经母细胞瘤的分期增加和高风险呈正相关。最重要的是,敲低 PCLAF 可以限制神经母细胞瘤细胞在体外和体内的增殖。通过分析 RNA-seq 数据,我们发现在降低 PCLAF 表达后,差异表达下调基因中细胞周期相关通路基因的富集最为显著。此外,PCLAF 通过激活 E2F1/PTTG1 信号通路加速神经母细胞瘤细胞周期的 G1/S 转换。在这项研究中,我们揭示了 PCLAF 促进细胞周期进程的机制,并建议 PCLAF/E2F1/PTTG1 轴是神经母细胞瘤的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6d9/8873510/ea3ddb716a19/41419_2022_4635_Fig1_HTML.jpg

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