E26 transformation (ETS)‑specific related transcription factor‑3 (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer

Abstract

Thyroid cancer is the most commonly diagnosed malignancy of the endocrine system, the incidence of which has increased rapidly in the last 30 years. Genetic alterations in pathways, including the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathways, are the driving force behind the development of differentiated thyroid cancer cases into aggressive and undifferentiated forms of thyroid cancer. E26 transformation (ETS)-specific related transcription factor-3 (ELF3) belong to the epithelial-specific subfamily of ETS transcription factors and has recently been reported to be involved in various pathophysiological processes. However, the role of ELF3 in thyroid cancer has not yet been investigated. In the present study, data from The Cancer Genome Atlas (TCGA) were analyzed, and it was revealed that ELF3 was overexpressed in patients with papillary thyroid cancer (PTC). Furthermore, the expression of ELF3 was found to be higher in thyroid cancer tissues with a B-Raf proto-oncogene (BRAF) mutation as determined by western blot analysis and IHC staining. Additionally, ELF3 overexpression predicted a poor prognosis in patients with PTC. The MAPK signaling pathway inhibitor PLX4032 was demonstrated to strongly attenuate ELF3 protein levels in BRAF-mutant thyroid cancer cell lines. Knockdown of ELF3 with small interfering RNA (siRNA) inhibited the growth, clone formation, migration and invasion of BRAF mutant thyroid cancer cells. Mechanistically, ELF3 modulated the activity of the MAPK/Erk pathway via transcriptional regulation of the human epidermal growth factor receptor 2 family of receptors as determined by RT-qPCR. In conclusion, the present study demonstrated ELF3 to be a potential prognostic marker for patients with thyroid cancer. Notably, ELF3 was demonstrated to form a positive feedback loop with MAPK pathways leading to the progression of BRAF-mutant thyroid cancer.

PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival

“…A light microscope (Olympus Corp.) was used to capture images to observe sample staining. To analyze the expression of PTPN1, the staining was categorized as previously described (11) and was confirmed by a pathologist at the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine.…”

Peripheral Blood RNA Sequencing Unravels a Differential Signature of Coding and Noncoding Genes by Types of Kidney Allograft Rejection

“…Out of the different noncoding genes, we highlight ELF3, TADA3, TP53BP1, UP21, and SIGLEC17P that are upregulated in AMR and connected with the AKT1 and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. [39][40][41][42][43][44] Moreover, while TP53BP1 has been described to bind to p53 and play a key role in the repair of double-strand DNA breaks, it has also been shown to play a key role in Ig class-switch recombination during antibody genesis, 43,44 a key feature for DSA formation. We have inferred the noncoding genes' functionality based on the idea of co-expression as has been previously done by other authors, [33][34][35] although the fact that coding and noncoding gene are associated does not imply a common biological function.…”

Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma

“…ALOX5 had been reported to be highly expressed in PTC compared with normal tissues and was related to PTC tumor invasion (Kummer et al, 2012;Reyes et al, 2019). ELF3 was reported to be overexpressed with poor prognosis in PTC patients and likely function as an oncogene in TC (Chen et al, 2019). As for BTN-specific SEadjacent genes identified in this study, SLCO2A1 was reported to be downregulated in follicular thyroid cancer than benign adenoma (Pfeifer et al, 2013), suggesting its role in thyroid tumor pathogenesis.…”