{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Keratin 81 (KRT81) is a type II hair keratin primarily known for its structural role in the formation and integrity of hard keratinized tissues such as hair, nails, and claws. In the context of normal development, KRT81 is one among several hard keratins whose proper expression is essential for hair shaft formation, as evidenced by its identification in human hair follicles and its cloning from hair‐specific keratin gene studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Inherited mutations in hard keratin genes that include KRT81 have been linked to disorders such as monilethrix, where altered keratin structure underlies hair fragility and scarring alopecia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical role in hair differentiation, KRT81 has emerged as an important player in cancer biology. Functional studies in breast cancer cells indicate that full‐length KRT81 is expressed not only in normal mammary epithelial cells but also in cancer cells, where it contributes to processes such as cell migration and invasion. Specifically, knockdown of KRT81 leads to a reduction in matrix metalloproteinase (MMP9) activity and diminishes the migratory and invasive capacities of breast cancer cell lines, suggesting that KRT81 supports the aggressiveness of malignant cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In lung and hematologic malignancies, single nucleotide polymorphisms (SNPs) in the 3′ untranslated region of KRT81 (notably rs3660) have been shown to influence its expression and correlate with patient survival and disease recurrence. In non‐small‐cell lung cancer, for instance, the rs3660 genotype is not only associated with significant differences in time to recurrence but is also linked to distinct immunohistochemical profiles, particularly in squamous cell carcinomas, thereby highlighting its prognostic relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in multiple myeloma, reduced KRT81 protein levels (associated with certain allelic variants) correlate with lower cell proliferation in vitro."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although some studies indicate that the overall expression levels of major hair keratins such as KRT81 remain unaltered in conditions such as radiation-induced alopecia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", the evidence collectively supports a dual role for KRT81: as a critical structural protein in keratinized tissues under physiological conditions and as a modulator of cell behavior in pathological settings, including cancer. This dual functionality emphasizes that alterations in KRT81 expression or genetic variation can influence not only tissue differentiation and integrity but also key aspects of tumor cell invasion, migration, and prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "P E Bowden, S Hainey, G Parker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence and expression of human hair keratin genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (1994)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/0923-1811(94)90046-9"}], "href": "https://doi.org/10.1016/0923-1811(94"}, {"type": "t", "text": "90046-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7528047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7528047"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maurice van Steensel, Maaike Vreeburg, Maria T Urbina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel KRT83 and KRT86 mutations associated with monilethrix."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.12624"}], "href": "https://doi.org/10.1111/exd.12624"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25557232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25557232"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Naoki Nanashima, Kayo Horie, Toshiyuki Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hair keratin KRT81 is expressed in normal and breast cancer cells and contributes to their invasiveness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5564"}], "href": "https://doi.org/10.3892/or.2017.5564"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28405679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28405679"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marc Campayo, Alfons Navarro, Nuria Viñolas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A dual role for KRT81: a miR-SNP associated with recurrence in non-small-cell lung cancer and a novel marker of squamous cell lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0022509"}], "href": "https://doi.org/10.1371/journal.pone.0022509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21799879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21799879"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "S Y Lee, J E Choi, H S Jeon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdv100"}], "href": "https://doi.org/10.1093/annonc/mdv100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25716425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25716425"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Carlos Fernández de Larrea, Alfons Navarro, Rut Tejero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of MiRSNPs on survival and progression in patients with multiple myeloma undergoing autologous stem cell transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-12-0191"}], "href": "https://doi.org/10.1158/1078-0432.CCR-12-0191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22539802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22539802"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Naoki Nanashima, Koichi Ito, Takashi Ishikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Damage of hair follicle stem cells and alteration of keratin expression in external radiation-induced acute alopecia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2012.1018"}], "href": "https://doi.org/10.3892/ijmm.2012.1018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22692500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22692500"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chang-Yi Cui, Joakim Klar, Patrik Georgii-Heming, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frizzled6 deficiency disrupts the differentiation process of nail development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2013.84"}], "href": "https://doi.org/10.1038/jid.2013.84"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23439395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23439395"}]}]}]}