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PAFAH1B3的异常表达影响骨肉瘤的增殖和凋亡。

Aberrant Expression of PAFAH1B3 Affects Proliferation and Apoptosis in Osteosarcoma.

作者信息

Fan Jian, Yang Yi, Qian Ji-Kui, Zhang Xin, Ji Jia-Qing, Zhang Li, Li Shan-Zhu, Yuan Feng

机构信息

Department of Orthopedics, Tongji Hospital, Tongji University, Shanghai, China.

出版信息

Front Oncol. 2021 May 31;11:664478. doi: 10.3389/fonc.2021.664478. eCollection 2021.

Abstract

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. , 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 . 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 , and also suppressed osteosarcoma growth . 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.

摘要

骨肉瘤是一种主要的骨与软组织恶性肿瘤,具有早期转移和高死亡率的特点。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,已发现在几种癌症类型的肿瘤发生和侵袭性中起关键作用。然而,PAFAH1B3在骨肉瘤进展中的作用和调控机制仍不清楚。通过免疫组织化学检测了83例骨肉瘤组织和44例配对的相邻正常骨组织中PAFAH1B3的表达。进行功能丧失实验以探究PAFAH1B3在骨肉瘤细胞中的作用。采用肿瘤异种移植生长实验来验证敲低PAFAH1B3对骨肉瘤生长的影响。进行芯片实验以研究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,敲低PAFAH1B3可抑制骨肉瘤细胞增殖并促进凋亡,还可抑制骨肉瘤生长。此外,PAFAH1B3在骨肉瘤中的增殖作用与EIF4EBP1、MYC、PTGS2和RPS6KB1表达的调控有关。本研究证明了PAFAH1B3对骨肉瘤增殖的生物学功能。该研究表明PAFAH1B3可能是骨肉瘤患者的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d67/8201501/7c9f8bb3476f/fonc-11-664478-g001.jpg

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