Aberrant Expression of PAFAH1B3 Affects Proliferation and Apoptosis in Osteosarcoma

被引:10
作者
Fan, Jian [1 ]
Yang, Yi [1 ]
Qian, Ji-kui [1 ]
Zhang, Xin [1 ]
Ji, Jia-qing [1 ]
Zhang, Li [1 ]
Li, Shan-zhu [1 ]
Yuan, Feng [1 ]
机构
[1] Tongji Univ, Tongji Hosp, Dept Orthoped, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
osteosarcoma; cell proliferation; apoptosis; therapeutic target; PLATELET-ACTIVATING-FACTOR; FACTOR ACETYLHYDROLASE; METABOLISM; SUBUNIT; PROGNOSIS; 1B3;
D O I
10.3389/fonc.2021.664478
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:11
相关论文
共 29 条
[1]   A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer [J].
Braunstein, Steve ;
Karpisheva, Ksenia ;
Pola, Carolina ;
Goldberg, Judith ;
Hochman, Tsivia ;
Yee, Herman ;
Cangiarella, Joan ;
Arju, Rezina ;
Formenti, Silvia C. ;
Schneider, Robert J. .
MOLECULAR CELL, 2007, 28 (03) :501-512
[2]   A network-based analysis of systemic inflammation in humans [J].
Calvano, SE ;
Xiao, WZ ;
Richards, DR ;
Felciano, RM ;
Baker, HV ;
Cho, RJ ;
Chen, RO ;
Brownstein, BH ;
Cobb, JP ;
Tschoeke, SK ;
Miller-Graziano, C ;
Moldawer, LL ;
Mindrinos, MN ;
Davis, RW ;
Tompkins, RG ;
Lowry, SF .
NATURE, 2005, 437 (7061) :1032-1037
[3]   Selective Inhibitor of Platelet-Activating Factor Acetylhydrolases 1b2 and 1b3 That Impairs Cancer Cell Survival [J].
Chang, Jae Won ;
Zuhl, Andrea M. ;
Speers, Anna E. ;
Niessen, Sherry ;
Brown, Steven J. ;
Mulvihill, Melinda M. ;
Fan, Yi Chiao ;
Spicer, Timothy P. ;
Southern, Mark ;
Scampavia, Louis ;
Fernandez-Vega, Virneliz ;
Dix, Melissa M. ;
Cameron, Michael D. ;
Hodder, Peter S. ;
Rosen, Hugh ;
Nomura, Daniel. K. ;
Kwon, Ohyun ;
Hsu, Ku-Lung ;
Cravatt, Benjamin F. .
ACS CHEMICAL BIOLOGY, 2015, 10 (04) :925-932
[4]  
Felciano Ramon M, 2013, Pac Symp Biocomput, P17
[5]   In vivo RNAi screening identifies Pafah1b3 as a target for combination therapy with TKIs in BCR-ABL1+ BCP-ALL [J].
Fiedler, Eleanor R. C. ;
Bhutkar, Arjun ;
Lawler, Emily ;
Besada, Rana ;
Hemann, Michael T. .
BLOOD ADVANCES, 2018, 2 (11) :1229-1242
[6]   Cyclooxygenase-2 in cancer: A review [J].
Goradel, Nasser Hashemi ;
Najafi, Masoud ;
Salehi, Eniseh ;
Farhood, Bagher ;
Mortezaee, Keywan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (05) :5683-5699
[7]   An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients [J].
Gyoerffy, Balazs ;
Lanczky, Andras ;
Eklund, Aron C. ;
Denkert, Carsten ;
Budczies, Jan ;
Li, Qiyuan ;
Szallasi, Zoltan .
BREAST CANCER RESEARCH AND TREATMENT, 2010, 123 (03) :725-731
[8]   PURIFICATION AND CHARACTERIZATION OF PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE-II FROM BOVINE LIVER CYTOSOL [J].
HATTORI, K ;
HATTORI, M ;
ADACHI, H ;
TSUJIMOTO, M ;
ARAI, H ;
INOUE, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (38) :22308-22313
[9]   Cloning and expression of a cDNA encoding the beta-subunit (30-kDa subunit) of bovine brain platelet-activating factor acetylhydrolase [J].
Hattori, M ;
Adachi, H ;
Aoki, J ;
Tsujimoto, M ;
Arai, H ;
Inoue, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (52) :31345-31352
[10]  
HATTORI M, 1994, J BIOL CHEM, V269, P23150