Aberrant Expression of PAFAH1B3 Affects Proliferation and Apoptosis in Osteosarcoma.

Aberrant Expression of PAFAH1B3 Affects Proliferation and Apoptosis in Osteosarcoma.
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PAFAH1B3 的异常表达影响骨肉瘤的增殖和凋亡

DOI:
10.3389/fonc.2021.664478
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发表时间:
2021
影响因子:
4.7
通讯作者:
Yuan F
Yuan F
中科院分区:
医学3区
文献类型:
--
作者:
Fan J;Yang Y;Qian JK;Zhang X;Ji JQ;Zhang L;Li SZ;Yuan F

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骨肉瘤是一种主要的骨和软组织恶性肿瘤,具有转移早、死亡率高的特点。血小板活化因子乙酰水解酶1B3 (PAFAH1B3)是一种与癌症相关的分子,在几种癌症类型的肿瘤发生和侵袭中起着至关重要的作用。然而,PAFAH1B3在骨肉瘤进展中的作用和调节机制尚不清楚。免疫组化检测83例骨肉瘤组织和44对相邻正常骨组织中PAFAH1B3的表达。在体外,通过功能缺失实验来探索PAFAH1B3在骨肉瘤细胞中的作用。采用肿瘤异种移植物生长试验验证PAFAH1B3基因敲低对骨肉瘤体内生长的影响。采用芯片法研究PAFAH1B3调控骨肉瘤增殖的机制。PAFAH1B3在骨肉瘤组织和细胞系中过表达。此外,PAFAH1B3基因敲低可抑制体外骨肉瘤细胞增殖,促进细胞凋亡,并抑制体内骨肉瘤生长。此外,PAFAH1B3在骨肉瘤中的增殖作用与调控EIF4EBP1、MYC、PTGS2和RPS6KB1的表达有关。本研究证实了PAFAH1B3对骨肉瘤增殖的生物学功能。本研究提示PAFAH1B3可能成为骨肉瘤患者新的治疗靶点。
Osteosarcoma is a major malignant tumor of bone and soft tissue, which is presenting with early metastasis and a high mortality rate. Platelet activating factor acetylhydrolase 1B3 (PAFAH1B3), a cancer-relevant molecular, was found to play a vital role in tumorigenesis and aggressiveness in several cancer types. However, the roles and the regulating mechanisms of PAFAH1B3 in osteosarcoma progression remain unclear. PAFAH1B3 expression was detected by immunohistochemistry in 83 osteosarcoma tissues and 44 paired adjacent normal bone tissues. In vitro, loss-of-function assay was performed to explore the role of PAFAH1B3 in osteosarcoma cells. Tumor xenograft growth assay was used to verify the effect of PAFAH1B3 knockdown on osteosarcoma growth in vivo. Chip assay was carried out to investigate the mechanism in osteosarcoma proliferation regulated by PAFAH1B3. PAFAH1B3 was overexpressed in osteosarcoma tissues and cell lines. Moreover, PAFAH1B3 knockdown inhibited osteosarcoma cell proliferation and promoted apoptosis in vitro, and also suppressed osteosarcoma growth in vivo. Furthermore, the proliferative effect of PAFAH1B3 in osteosarcoma was related to the regulation of the expression of EIF4EBP1, MYC, PTGS2 and RPS6KB1. This study demonstrated the biological function of PAFAH1B3 on osteosarcoma proliferation. This research suggested that PAFAH1B3 could be a novel therapeutic target for osteosarcoma patients.
DOI: 10.1016/j.cell.2009.11.027
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