JAZF1 Suppresses Papillary Thyroid Carcinoma Cell Proliferation and Facilitates Apoptosis via Regulating TAK1/NF-κB
Liangliang Huang1, Yuhuai Cai1, Yi Luo1
1Medical Center of Breast and Thyroid Disease, Affiliated Hospital of ZunYi Medical University, ZunYi, Guizhou 563003, People's Republic of China.
Purpose:
Juxtaposed with another zinc finger gene 1 (JAZF1) is involved in gluconeogenesis, insulin sensitivity, cell differentiation, lipid metabolism and inflammation, but its role in carcinoma remains inexplicit.
Patients And Methods:
We explored the JAZF1 expression in human papillary thyroid cancer (PTC) tissues, adjacent normal thyroid tissues and nodular goitre tissues, as well as Ki67 expression in PTC tissues, using immunohistochemistry staining. Western blotting and RT-qPCR were performed to explore the JAZF1 expression levels in Nthy-ori 3-1, BCPAP and TPC-1 cells. BCPAP cells overexpressing JAZF1 were constructed using an Adv-JAZF1-GFP recombinant adenovirus vector. Next, the cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis and immunofluorescence were performed. The mRNA expression level of nuclear factor-κB p65 (NF-κB p65) was examined using RT-qPCR. The expression of Bcl-2, Bax, transforming growth factor beta-activated kinase 1 (TAK1), NF-κB p65 and NF-κB p-p65 were examined using Western blotting.
Results:
The expression of JAZF1 in human PTC tissues was downregulated compared with adjacent thyroid tissues or nodular goitre. Additionally, JAZF1 expression was associated with the location and lymph node metastasis of PTC. The expression level of JAZF1 had a negative correlation with Ki67 labelling index (LI). Compared to Nthy-ori 3-1 cells and TPC-1 cells, BCPAP cells expressed the lowest JAZF1. JAZF1 overexpressed significantly inhibited proliferation, caused G0/G1 cell cycle arrest and promoted apoptosis in BCPAP cells. Furthermore, JAZF1 overexpressed in BCPAP cells clearly upregulated the expression level of Bax protein, whereas decreased the expression of Bcl-2, TAK1, NF-κB but did not affect the mRNA or protein expression level of NF-κB p65.
Conclusion:
JAZF1 inhibits proliferation and induces apoptosis in BCPAP cells by suppressing the activation of TAK1/NF-κB signalling pathways, suggesting that JAZF1 may serve as a reliable molecular marker in PTC.
Insights
Juxtaposed with another zinc finger gene 1 (JAZF1) is downregulated in papillary thyroid cancer (PTC). Overexpressing JAZF1 inhibits PTC cell proliferation and induces apoptosis by suppressing TAK1/NF-κB signaling, suggesting JAZF1 as a potential PTC marker.
Area of Science:
- Molecular biology
- Cancer research
- Endocrinology
Background:
- Juxtaposed with another zinc finger gene 1 (JAZF1) plays roles in various cellular processes but its function in carcinoma is unclear.
- Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, necessitating research into novel molecular markers and therapeutic targets.
Purpose of the Study:
- To investigate the expression and function of JAZF1 in human papillary thyroid cancer (PTC).
- To explore the potential of JAZF1 as a diagnostic marker and therapeutic target in PTC.
Main Methods:
- Immunohistochemistry, Western blotting, and RT-qPCR were used to assess JAZF1 expression in PTC tissues and cell lines.
- Functional assays including cell proliferation, colony formation, cell cycle, and apoptosis analyses were performed in JAZF1-overexpressing BCPAP cells.
- The study examined the impact of JAZF1 on the TAK1/NF-κB signaling pathway.
Main Results:
- JAZF1 expression was significantly downregulated in PTC tissues compared to adjacent normal tissues and nodular goitres.
- JAZF1 expression levels negatively correlated with Ki67 labelling index and were associated with tumor location and lymph node metastasis.
- Overexpression of JAZF1 in BCPAP cells inhibited proliferation, induced G0/G1 cell cycle arrest, promoted apoptosis, and suppressed TAK1/NF-κB signaling.
Conclusions:
- JAZF1 inhibits PTC cell proliferation and induces apoptosis by suppressing the TAK1/NF-κB signaling pathway.
- JAZF1 may serve as a valuable molecular marker for the diagnosis and potentially the treatment of PTC.
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