{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSOX15 is emerging as a multifaceted transcription factor with important tumor‐suppressive properties. In pancreatic cancer, for example, SOX15 appears to function as a candidate tumor suppressor whose reduced expression—via DNA hypermethylation, deletion, or mRNA downregulation—is associated with enhanced tumor cell viability, and its reexpression inhibits cancer cell growth by suppressing oncogenic Wnt/β‑catenin signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, enforced SOX15 expression in NT2/D1 cells leads to marked slowing of cell proliferation with accumulation in the G1‑G0 phase and upregulation of a set of cell cycle–related genes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and in thyroid carcinoma settings, aberrant regulation by miR‑147b results in reduced SOX15 levels, contributing to enhanced proliferation and invasion; restoration of SOX15 reverses these malignant features by downregulating Wnt/β‑catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in curbing tumor cell proliferation, SOX15 influences a range of processes that impact cell fate and cancer progression. In prostate cancer, SOX15 transcriptionally upregulates AOC1 expression, leading to downstream activation of reactive oxygen species and ferroptosis, thereby inhibiting tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, studies indicate that SOX15 can activate genes such as NR5A1, integrating it into broader regulatory networks that govern embryonic development and cellular differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Its potential tumor suppressor role is further being explored in colorectal cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In parallel, characterization of stemness-related factors in endometrial-derived cells, as seen in investigations of endometriosis, has highlighted the presence and distribution of SOX15 along with other markers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, in glioblastoma, a novel regulatory mechanism has been described in which the circular RNA circVPS8 acts as a scaffold promoting MKRN1-mediated ubiquitination and degradation of SOX15, a process that, together with parallel changes in HNF4A expression, inhibits ferroptosis and facilitates tumor progression; complementary studies have also assessed SOX15 promoter methylation in thyroid tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K L Thu, N Radulovich, D D Becker-Santos, et al. 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