Fra-1 promotes thyroid cancer progression by activating the pentose phosphate pathway through the upregulation of YWHAH expression

The incidence of thyroid cancer has been on a continuous upward trend in recent years, and some patients with advanced thyroid cancer have poor clinical treatment results. Therefore, it is of great significance to explore the molecular mechanisms of malignant progression in thyroid cancer and to identify new molecular targets. The transcription factor Fra-1 is closely related to processes such as tumor cell proliferation, apoptosis, and invasion, and is involved in the development of many malignant tumors. In this study, we first found that high expression of Fra-1 activates the pentose phosphate pathway in thyroid cancer cells through energy metabolomics. Secondly, we screened and identified YWHAH as a key gene downstream of Fra-1 using whole-transcriptome analysis, and confirmed that Fra-1 binds to the promoter region of YWHAH and positively regulates its expression using ChIP-qPCR experiments. Then, rescue experiments were further used to show that YWHAH functions as an important downstream mediator through which Fra-1 activates the pentose phosphate pathway and thereby affects thyroid cancer progression. Taken together, the present study confirms that Fra-1 activates the pentose phosphate pathway (PPP) by binding to the promoter region of YWHAH and upregulating its expression, which in turn promotes malignant progression of thyroid cancer. The results of this study will help to elucidate the role of Fra-1 in the development of differentiated thyroid cancer and the related mechanisms, which will be of positive significance for elucidating the pathogenesis of thyroid cancer and for discovering potential therapeutic targets.