{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in glioma have revealed that SOX21, a transcription factor acting in opposition to SOX2, plays an important role in modulating tumor cell behavior. In human glioma cells, co‐expression of SOX21 with SOX2 and differentiation markers such as GFAP is observed, and experimental overexpression of SOX21 leads to reduced cell proliferation, induction of apoptosis, and a shift toward differentiation. These findings suggest that SOX21 functions as a negative regulator of SOX2, thereby suppressing the stem‐like, proliferative state in glioma and contributing to tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in malignant contexts, SOX21 is also critical during normal neural and airway development. In early neural regionalization, loss of SOX21 results in aberrant activation of Wnt signaling and a caudalization of rostral forebrain neural progenitors—an effect mediated in part by de-repression of WNT8B. Similarly, in the developing airway epithelium, SOX21 is co-expressed with SOX2 in a defined progenitor zone and acts to temper SOX2-induced differentiation, thereby maintaining a balanced progenitor state that is essential for proper patterning and regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA related but distinct molecular entity emerging from the SOX21 locus is the long non-coding RNA (lncRNA) SOX21-AS1. Dysregulation of SOX21-AS1 has been documented in several cancers where it appears to function as an oncogenic facilitator. In colorectal cancer, for example, overexpression of SOX21-AS1 promotes proliferation and invasion via modulation of the miR-145/MYO6 axis. Similar tumor-promoting roles are observed in hepatocellular carcinoma and nephroblastoma, where elevated SOX21-AS1 levels correlate with poor clinical outcomes; recent work in pancreatic cancer further underscores the broad relevance of SOX21-AS1 in tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdding to the clinical significance of the SOX21 locus, epigenetic alterations of the SOX21 gene itself—specifically, promoter methylation detectable in stool DNA—have been proposed as a noninvasive biomarker for colorectal cancer screening, illustrating the multifaceted impact of SOX21-related mechanisms in both development and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Ferletta, Demet Caglayan, Liza Mokvist, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2019.10.013"}], "href": "https://doi.org/10.1016/j.stemcr.2019.10.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31761677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31761677"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Evelien Eenjes, Dick Tibboel, Rene M H Wijnen, et al. 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