Transcriptionally up-regulation of CDKN1A/p21 by TFE3 fusion proteins worsened TFE3-rearranged renal cell carcinoma
Year: 2025
Type: article
Abstract: The TFE3-rearranged renal cell carcinoma (TFE3-rRCC), which is an uncommon and aggressive form of kidney cancer, has an unfavorable prognosis. It has been shown that CDKN1A/p21 is high-expressed in TFE3-rRCC, however, the exact mechanism and the role of CDKN1A/p21 in TFE3-rRCC remain unclear. Our results indicated that the TFE3 fusions exacerbated TFE3-rRCC by transcriptionally upregulating CDKN1A/p21 expression. In terms of the mechanism, CDKN1A/p21 was a target gene of TFE3 fusions with positive regulation. Activation of AKT led to the cytoplasmic localization of highly expressed CDKN1A/p21, promoting TFE3-rRCC progression by anti-apoptosis and facilitating migration. Additionally, the remaining nuclear CDKN1A/p21 induced cellular senescence (CS) and secretion of senescence-associated secretory phenotype (SASP) factors, particularly IL-6 and IL-8, which recruited inhibitory immune cells and remodeled tumor microenvironment. This research presents that upregulation of CDKN1A/p21 transcriptionally by TFE3 fusions facilitates the progression of TFE3-rRCC by inducing anti-apoptosis, migration and CS, thus provides a promising target for treating TFE3-rRCC.
Source: Scientific Reports
Institutions: Nanjing Drum Tower Hospital, First Affiliated Hospital of Zhengzhou University, Nanjing University, Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing University of Chinese Medicine, Nantong University, Affiliated Hospital of Nantong University, Nanjing First Hospital, State Key Laboratory of Analytical Chemistry for Life Science
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Award: G6952577892
OpenAlex ID: W4413309030