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Published on: August 23, 2019
NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer
Cen Jiang1, Jianli He1, Sunwang Xu2
1State Key Laboratory of Oncogenes and Related Genes, Renji Hospital Affiliated; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Abstract:
The morbidity of papillary thyroid cancer (PTC) is on the rise, but its pathogenesis is still poorly understood. NR4A1 is a transcription factor primarily involving a wide range of pathophysiological responses, but its relationship with PTC malignancy remains unclear. This study demonstrates that high NR4A1 expression is strongly associated with poor survival outcomes in PTC patients. The depletion of NR4A1 significantly inhibited the proliferation of PTC cells by negating the LEF1-mediated oncogenic alteration. Mechanistically, NR4A1 directly binds to the promoter region of LEF1 and leads to crosstalk with histone acetylation and DNA demethylation to transcriptionally upregulate LEF1 expression, subsequently promoting downstream growth-related genes expressions in PTC. In the light of our findings, NR4A1 may be an emerging driving factor in PTC pathogenesis and progression.
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