Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.

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Objectives. The standardized residency training (SRT) program in China is an important link for continuing education and clinical work training for graduate students. The purpose of our study was to enable educators to maintain the effectiveness of hysteroscopy teaching techniques and make the standardized residency training students well experienced in surgery, thus demonstrating that higher efficiency of teaching can lead to better proficiency for surgery. Methods. We generated resident-as-teacher teaching round and tutor guided hysteroscopic surgery as well as a questionnaire based on the mastery degree of the basic theoretical knowledge and operational skills of hysteroscopy among seven junior residents and five senior residents of the Obstetrics and Gynecology Department, including four attending gynecologic surgeons of a hysteroscopy teaching program. Results. Senior residents felt confident to teach, while junior residents learned effectively through the teaching round. There were statistically significant differences in the whole operation time and the volume of distension fluid used between junior and senior residents (p<0.05). Conclusions. This study acknowledges the need for new approaches to medical education for better characterization of the link between the use of teaching rounds through problem-based learning (PBL) discussion dominated by the residents themselves and overall surgical skills of teaching and learning.