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

Abstract

PurposeJuxtaposed 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 methodsWe 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.ResultsThe 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.ConclusionJAZF1 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.

TFAP2B, AP-1 and JAZF1 Expression in Tissues of Papillary Thyroid Carcinoma Patients; Clinical, Pathological and Prognostic Values

“…We showed that JAZF1 was down-regulated in papillary thyroid cancer tissues more than adjacent nonneoplastic tissues, which was similar to results of Huang et al, (2019), whose report was the first in exploring tumor suppressor role of JAZF1 in papillary thyroid carcinoma using immunohistochemistry and they stated that expression of JAZF1 in papillary thyroid carcinoma was decreased in comparison with adjacent thyroid tissues or with nodular goiter. Huang et al, (2019), showed that JAZF1 expression is inversely associated with Ki67 labelling index in cancer cells denoting that JAZF1 made its tumor suppressor function by inhibition of cell proliferation and cell cycle arrest. Yuasa et al, (2015) found different results, showed that increased JAZF1 expression increased cell proliferation and leads to the progression of the cell cycle, which stimulated oncogenesis in muscle.…”

“…Thyroid cancer is considered the most prevalent endocrine system cancers that continued rising worldwide in the past decades (Xiao et al, 2019). Papillary carcinoma of the thyroid formed about 74-80% of all thyroid malignancies (Huang et al, 2019). Papillary thyroid cancer has a favourable patients outcome and better patients survival, but it was found that some patients might have more aggressive phenotypes with lack of response to the currently used therapies with high patients morbidity and mortality (Fu et al, 2019).…”

The prediction of survival in Gastric Cancer based on a Robust 13-Gene Signature

“…In addition, ZBTB10 was regarded to regulate specificity proteins (Sp) by reactive oxygen species (ROS)- microRNA27a 25 . Chen et al proposed that JAZF1 suppresses proliferation and induces apoptosis via TAK1/NF-κB pathways 26 . DCBLD2 over-expression has been implicated in causing tumorigenesis, invasion and metastasis in colorectal cancer expression 27 .…”

Jazf1 acts as a regulator of insulin‐producing β‐cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice

“…An increase in proliferative capacity when Jazf1 is overexpressed has been reported in several studies, such as in prostate cancer cells, cardiac microvascular endothelial cells, C2C12 cells, and mouse airway epithelial cells [19,30–32]. It has also been reported that Jazf1 inhibits proliferation in cancer cells but not in normal cells [33]. In a study of cardiac microvascular cells, Jazf1 promoted proliferation and angiogenesis via the Akt signaling pathway [30].…”