TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway

Abstract

Thyroid cancer is commonly seen in the clinic with a rapidly increasing incidence globally. COX-2 overexpression correlates with the pathologic type of thyroid carcinoma, and it has been suggested that COX-2 overexpression is associated with a poor prognosis. However, little is known about its upstream regulatory mechanism. Bioinformatics suggested that transcription factor AP-2 beta (TFAP2B) might specifically bind to the COX-2 promoter, which was confirmed by biotin-labeled COX-2 promoter pulldown and luciferase reporter assays. We performed western blot and immunohistochemical staining to detect the expression of TFAP2B/COX-2 in thyroid cancer tissues (T) and the matched adjacent noncarcinoma tissues (ANT), and investigated the relationship between TFAP2B/COX-2 expression and clinical pathological factors in thyroid cancer patients. Afterward, MTS, colony formation, cell-apoptosis assay, transwell-invasion and scratch assays were performed to examine the proliferation, apoptosis, invasion, and migration of thyroid cancer cells with TFAP2B knocked down or overexpressed. The mouse xenograft experiment was performed to study in vivo the proliferation of thyroid cancer cells with TFAP2B knocked down or overexpressed. We found that TFAP2B bound to the promoter of COX-2 to activate its expression. Western blot and immunohistochemistry showed that TFAP2B/COX-2 was highly expressed in thyroid cancer, and high TFAP2B and COX-2 expression was associated with aggressive clinicopathological features in thyroid cancer. TFAP2B mediated thyroid cancer cell proliferation, apoptosis, invasion, and migration via the COX-2 signaling pathway in vitro and in vivo. TFAP2B bound to the promoter of COX-2 to activate its expression, indicating that TFAP2B is a critical regulatory molecule in the COX-2 signaling pathway that promoted tumor progression in thyroid cancer.

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

“…It is essential to detect novel valid therapeutic target for papillary thyroid cancer mainly for cases resistant to currently used therapies. In our study, we found that TFAP2B expression was elevated in cells of papillary thyroid cancer in comparison to adjacent non-neoplastic thyroid tissues which are similar to results of Fu et al, (2019), in papillary thyroid cancer and Fu et al, (2014) in lung cancer. Fu et al, (2019) showed that TFAP2B expression in lung cancer tumor tissue samples is markedly elevated in comparison to healthy tissues.…”

“…Moreover, Fu et al, (2019), stated that knocking down TFAP2B in cell lines of thyroid cancer reduced viability, proliferation, migration, and invasion of cancer cells. In our study, we clarified that TFAP2B higher expression increased the growth of papillary thyroid cancer.…”

“…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). Therefore, identifying new mechanisms of cancer progression and novel molecular biomarkers might help in the identification of patients having a higher liability of papillary carcinoma of the thyroid recurrence and progression.…”

“…Therefore, identifying new mechanisms of cancer progression and novel molecular biomarkers might help in the identification of patients having a higher liability of papillary carcinoma of the thyroid recurrence and progression. Transcription factor activating protein 2 B (TFAP2 B) is a transcription factor that regulates many steps of embryogenesis, cell growth, apoptosis and recently oncogenesis and cancer progression RESEARCH ARTICLE TFAP2B, AP-1 and JAZF1 Expression in Tissues of Papillary Thyroid Carcinoma Patients; Clinical, Pathological and Prognostic Values (Xu et al, 2017, Fu et al, 2019. AP-1 is a transcription factor that is a downstream molecule of the MAPK signaling pathway, which is incriminated in controlling many cellular processes as cell growth, apoptosis and proliferation (Li et al, 2016).…”

DNA Methylation and Breast Cancer Risk: An Epigenome-Wide Study of Normal Breast Tissue and Blood

“…This gene has been shown to harbor aberrant methylation in primary breast tumors [25]. The TFAP2B gene codes for the transcription factor AP-2 beta, a sequence-specific DNA-binding protein that has been recognized as an oncogene that mediates cancer cell proliferation, apoptosis, invasion, and migration via the COX-2 signaling pathway in vitro and in vivo [26]. TFAP2B is also expressed in breast tissue, where it is thought to coordinate HER2 and ER [27] and has been associated with breast cancer prognosis [28].…”