{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Claudin‐23 (CLDN23) is a member of the claudin family that contributes to the formation and regulation of tight junctions in diverse epithelia. In studies of viral entry, CLDN23 has been shown not to mediate hepatitis C virus infection in target cells, in marked contrast to other claudins (such as CLDN6 and CLDN9) that support viral entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, stimulation of Toll‐like receptor 2 in human keratinocytes enhances the expression of key tight junction components including claudin‐23, suggesting a role for CLDN23 in skin barrier repair and the innate response to inflammatory challenges."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In gastrointestinal epithelia, particularly in the colon, CLDN23 is normally expressed in differentiated colonocytes. Its expression is driven, at least in part, by transcriptional networks involving factors such as Tcf7l2 and Hnf4α, which stimulate CLDN23 as part of a program of epithelial barrier differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In colorectal cancer (CRC), multiple independent studies have demonstrated that CLDN23 expression is significantly downregulated in tumor tissues compared with normal mucosa, and more pronounced reductions in CLDN23 correlate with shorter overall survival. Moreover, functional investigations suggest that loss of CLDN23 may facilitate cancer cell migration and metastasis. Epigenetic mechanisms are also implicated in this loss; for example, EZH2‐mediated histone modifications can silence CLDN23 expression in CRC, effects that are reversible upon EZH2 inhibition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Bioinformatic analyses of claudin gene structure further indicate that alternative open reading frames may play a role in regulating the levels or subcellular fate of CLDN23, although the precise implications for cell function remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, the current body of evidence supports a model in which CLDN23 functions as a component of the epithelial barrier in both skin and gastrointestinal tissues. Its appropriate expression appears critical for maintaining normal cell–cell adhesion and tissue homeostasis, while decreases in CLDN23 expression—mediated either genetically or epigenetically—may contribute to increased cellular motility and poorer clinical outcomes in colorectal cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aihua Zheng, Fei Yuan, Yanqin Li, et al. 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