{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐203 (miR‑203) is a key regulator in normal epithelial biology. In the skin, miR‑203 is highly expressed specifically in keratinocytes, where it is induced during terminal differentiation and helps limit the proliferative potential of basal progenitor cells by directly repressing targets such as ΔNp63 (e.g., studies in psoriasis and keratinocyte differentiation demonstrate its up‐regulation and dependency on PKC/AP‑1 signaling)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, in gingival and bronchial epithelia, miR‑203 modulates inflammatory responses—its induction in gingival epithelial cells upon microbial challenge and its dysregulated expression in asthma underscore its role in maintaining epithelial–immune homeostasis and proper wound repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, miR‑203 exerts context‐dependent functions that frequently converge on the suppression of tumorigenic processes. In several malignancies—including pancreatic, hepatocellular, bladder, colorectal, prostate, esophageal, cervical, and lung cancers—miR‑203 is frequently silenced via promoter hypermethylation or other regulatory mechanisms; its restoration inhibits cell proliferation, migration, invasion, and resistance to chemotherapy. Specifically, studies have shown that in pancreatic cancer elevated miR‑203 expression may correlate with aggressive behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma its epigenetic silencing promotes tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In bladder cancer, miR‑203—inducible by curcumin—is downregulated in tumors and functions as a tumor suppressor by targeting anti‐apoptotic factors such as bcl‑w and oncogenic kinases like Akt2 and Src."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": " In colorectal and prostate cancers, diminished miR‑203 levels are associated with enhanced epithelial‑mesenchymal transition (EMT), increased stemness, and metastatic potential—with identified targets including Akt2, EIF5A2, Bmi‑1, and regulators of MAPK and androgen receptor signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "19"}]}, {"type": "t", "text": " Similar tumor‐suppressing roles have been documented in prostate cell models and cervical as well as esophageal cancers via the targeting of EMT regulators like SNAI2 and oncogenes such as Ran."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "25"}]}, {"type": "t", "text": " In addition, serum profiling studies highlight the potential of miR‑203 as a noninvasive biomarker, while its dysregulation is linked to altered cell signaling in various cancers, including modulation of Bmi‑1 in cancer stem‐like cells, as well as effects on exosome‐mediated communication."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also points to a complex interplay between miR‑203 and long noncoding RNAs (lncRNAs) that further refines its regulatory impact in cancer and chemoresistance. In several studies, miR‑203 is found to be involved in regulatory feedback loops with lncRNAs such as HOTAIR, HCP5, MALAT1, and possibly UCA1, which modulate EMT, metastatic behavior, and drug response in tumors of the lung, brain, and kidney."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "36", "end_ref": "43"}]}, {"type": "t", "text": " These interactions, along with miR‑203’s direct targeting of kinases such as PKCα and SRC, elegantly illustrate its multifaceted roles in coordinating cellular differentiation, proliferation, apoptosis, EMT, and chemoresistance. Together, these findings underscore the potential of miR‑203 as both a prognostic biomarker and a therapeutic target across a spectrum of epithelial and malignant diseases.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Enikö Sonkoly, Tianling Wei, Peter C J Janson, et al. 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