JAZF1 Suppresses Papillary Thyroid Carcinoma Cell Proliferation and Facilitates Apoptosis via Regulating TAK1/NF-κB Pathways

Abstract

Liangliang Huang,1,* Yuhuai Cai,1,* Yi Luo,1 Daigang Xiong,1 Zeyu Hou,1 Junyuan Lv,1 Feng Zeng,1 Yan Yang,2,3 Xiaoming Cheng1 1Medical Center of Breast and Thyroid Disease, Affiliated Hospital of ZunYi Medical University, ZunYi, Guizhou 563003, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of ZunYi Medical University, ZunYi, Guizhou 563003, People’s Republic of China; 3College of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou 563003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoming ChengMedical Center of Breast and Thyroid Disease, Affiliated Hospital of ZunYi Medical University, 149 Dalian Road, ZunYi, Guizhou 563003, People’s Republic of ChinaTel [phone]Email [email protected] YangDepartment of Clinical Laboratory, Affiliated Hospital of ZunYi Medical University, 149 Dalian Road, ZunYi, Guizhou 563003, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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.Keywords: Juxtaposed with another zinc finger gene 1, papillary thyroid cancer, TAK1, NF-κB

Keywords

• juxtaposed with another zinc finger gene 1
• papillary thyroid cancer
• tak1
• nf-κb