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ARTICLE
EIF5A2 Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Growth by Modulating TGF-β Signals
Fengyun Hao*1, Qingli Zhu†, Lingwei Lu†, Shukai Sun‡, Yichuan Huang§, Jinna Zhang¶,
Zhaohui Liu†#, Yuanqing Miao**, Xuelong Jiao††, Dong Chen††1
* Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
† Department of Thyroid Surgery, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
‡ Department of Clinical Lab, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
§ Department of Otolaryngology, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
¶ Department of Medical Experiment Center, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
# Department of Molecular Biochemistry and Genetic Engineering, Shenzhen University, Shenzhen, P.R. China
** Department of Medical Network Information Center, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
†† Department of General Surgery, the Affiliated Hospital of Qingdao University, Qingdao, P.R. China
Oncology Research 2020, 28(4), 345-355. https://doi.org/10.3727/096504020X15834065061807
Abstract
Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic
translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression
status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis
in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues
and adjacent nontumorous tissues (ANCT) (n = 24) by immunochemistry. Expressions of EIF5A2 mRNA and
protein were analyzed in fresh-matched ATC and ANCT (n = 23) and ATC cell lines by real-time polymerase
chain reaction (PCR) and Western blotting. The effect of targeting EIF5A2 with short hairpin RNA (shRNA)
or EIF5A2 overexpression on the ATC tumorigenesis and TGF- /Smad2/3 signals in vitro and in vivo was
investigated. Expression of EIF5A2 was significantly upregulated in ATC tissues and cell lines compared
with ANCT and normal follicular epithelial cell line. Functional studies found that targeting EIF5A2 induced
SW1736 cell death in vitro and in vivo, followed by significantly downregulated phosphorylation of Smad2/3
(p-Smad2/3) in SW1736 cells at the protein level. Ectopic expression of EIF5A2 could promote 8505C cell
growth in vitro and in vivo, followed by significantly upregulated p-Smad3 at the protein level. Recombinant
human TGF- 1 (hTGF- 1) treatment decreased the antiproliferative activity of the EIF5A2 downexpressing
8505C cells through reversing pSmad2/3. Using the specific inhibitor SB431542 to block TGF- pathway or
Smad3 siRNA to knock down Smad3 increased the antiproliferative activity of the EIF5A2-overexpressing
8505C cells through inhibiting pSmad2/3. Our findings indicated that EIF5A2 controled cell growth in ATC
cells, and EIF5A/TGF- /Smad2/3 signal may be a potential therapeutic target for ATC treatment.
Keywords
Cite This Article
Hao, F., Zhu, Q., Lu, L., Sun, S., Huang, Y. et al. (2020). EIF5A2 Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Growth by Modulating TGF-β Signals.
Oncology Research, 28(4), 345–355. https://doi.org/10.3727/096504020X15834065061807