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Homeodomain transcription factors of the Sine oculis (SIX) family direct multiple regulatory processes throughout the metazoans. Sine oculis (So) was first characterized in the fruit fly Drosophila melanogaster, where it is both necessary and sufficient for eye development, regulating cell survival, proliferation, and differentiation. Despite its key role in development, only a few direct targets of So have been described previously. In the current study, we aim to expand our knowledge of So-mediated transcriptional regulation in the developing Drosophila eye using ChIP-seq to map So binding regions throughout the genome. We find 7,566 So enriched regions (peaks), estimated to map to 5,952 genes. Using overlap between the So ChIP-seq peak set and genes that are differentially regulated in response to loss or gain of so, we identify putative direct targets of So. We find So binding enrichment in genes not previously known to be regulated by So, including genes that encode cell junction proteins and signaling pathway components. In addition, we analyze a subset of So-bound novel genes in the eye, and find eight genes that have previously uncharacterized eye phenotypes and may be novel direct targets of So. Our study presents a greatly expanded list of candidate So targets and serves as basis for future studies of So-mediated gene regulation in the eye.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934907 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089695 | PLOS |
Oncogene
September 2025
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSCs) are pivotal in breast cancer mechanism research. It was demonstrated that Sine oculis homeobox homolog 1 (SIX1) orchestrates breast cancer EMT and BCSCs, concurrently activating the Signal transducer and activator of transcription 3 (STAT3) signaling pathway. Yet, the mechanism by which SIX1 modulates STAT3 and its potential to regulate EMT and BCSCs through STAT3 signaling remain unexplored.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
July 2025
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. Electronic address:
The SIX (Sine Oculis homeobox) gene family plays a crucial role in carcinogenesis and cancer therapy by encoding transcription factors that regulate a diverse array of downstream target genes through mechanisms of repression and activation. This review, founded on existing research and incorporating bioinformatics tools, summarizes the expression patterns, prognostic significance, functional roles, and underlying mechanisms of the SIX family across various tumor types. Additionally, it explores the impact of the SIX family in multiple cancer treatment approaches, including cancer chemotherapy, radiotherapy, targeted therapy, immunotherapy, and herbal or natural ingredient therapy.
View Article and Find Full Text PDFEvodevo
July 2025
Department of Biology, DeSales University, Center Valley, PA, USA.
Background: Evidence suggests that Pax6 genes are necessary for the specification of eyes in a variety of metazoans, including mandibulate arthropods. In these arthropods, Pax6 genes usually interact with a conserved set of genes, collectively called the retinal determination gene network (RDGN), to specify eye cells. However, recent data have argued that Pax6 genes lack a role in the development of the eyes in Chelicerata (= arachnids, horseshoe crabs, and sea spiders).
View Article and Find Full Text PDFCell Res
September 2025
School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Transcriptional control is crucial for the regulation of inflammation. While it is well-established that inducible transcriptional repressors are synthesized de novo through signal-dependent transcriptional upregulation, it remains unclear whether post-translational modification mechanisms, such as deubiquitination, also contribute to this process. We previously identified developmentally silenced sine oculis (SIX) transcription factors that are reactivated to control inflammatory gene transcription in differentiated immune cells under chronic microbial infections.
View Article and Find Full Text PDFCurr Med Sci
June 2025
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Objective: To investigate the combined effects of thymidine phosphorylase (TYMP) and sine oculis homeobox homologue 1 (Six1) on the tumor microenvironment and their role in promoting metastasis in gastric cancer (GC).
Methods: A total of 674 GC patients who underwent surgical resection were enrolled. Correlations between TYMP/Six1 expression and the clinicopathological characteristics and overall survival of patients were analysed.