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EIF5A2 Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Growth by Modulating TGF-
Fengyun Hao1, Qingli Zhu2, Lingwei Lu2
1Department of Pathology, the Affiliated Hospital of Qingdao UniversityQingdaoP.R. China.
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.
Insights
Eukaryotic translation initiation factor 5A2 (EIF5A2) is upregulated in anaplastic thyroid carcinoma (ATC). Targeting EIF5A2 inhibits ATC cell growth by affecting the TGF-/Smad2/3 pathway, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid cancer with limited treatment options.
- Eukaryotic translation initiation factor 5A2 (EIF5A2) is implicated in tumor metastasis and its role in ATC is not well understood.
Purpose of the Study:
- To investigate the expression of EIF5A2 in human ATC tissues and cell lines.
- To elucidate the role and underlying mechanisms of EIF5A2 in ATC tumorigenesis.
- To explore EIF5A2 as a potential therapeutic target for ATC.
Main Methods:
- Immunohistochemistry, real-time PCR, and Western blotting were used to analyze EIF5A2 expression in ATC tissues and cell lines.
- Short hairpin RNA (shRNA) and overexpression systems were employed to manipulate EIF5A2 levels in vitro and in vivo.
- The TGF-/Smad2/3 signaling pathway was assessed following EIF5A2 modulation.
Main Results:
- EIF5A2 expression was significantly upregulated in ATC tissues and cell lines compared to normal tissues.
- EIF5A2 knockdown induced cell death and downregulated p-Smad2/3 in SW1736 cells.
- EIF5A2 overexpression promoted cell growth and upregulated p-Smad3 in 8505C cells, with modulation of the TGF-/Smad2/3 pathway.
Conclusions:
- EIF5A2 plays a crucial role in controlling cell growth in ATC.
- The EIF5A2/TGF-/Smad2/3 signaling axis represents a promising therapeutic target for anaplastic thyroid carcinoma.
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