{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The histocompatibility‐associated protein 5 (HCP5), located within the major histocompatibility complex region, has emerged as a multifaceted determinant in human disease. On one level, genome‐wide analyses in HIV‐1 infection have repeatedly identified a key HCP5 single‐nucleotide polymorphism (rs2395029) that is in strong linkage disequilibrium with protective HLA alleles (such as HLA‐B*57) and is associated with lower viral set points, a smaller HIV reservoir, and delayed progression to AIDS (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, HCP5 genetic variants have been implicated in autoimmune and inflammatory conditions such as psoriasis, psoriatic arthritis, and even herpes zoster, supporting a role for this locus in viral suppression and immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role as a genetic marker in infection and autoimmunity, HCP5 also functions as a long noncoding RNA that can modulate key biological pathways in cancer and other disorders. In gastric cancer, mesenchymal stem cell–induced HCP5 promotes tumor cell stemness and chemoresistance by sequestering miR‐3619‑5p, which in turn activates an AMPK/PGC1α/CEBPB transcription complex that enhances fatty acid oxidation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In triple‐negative breast cancer, upregulated HCP5 acts as a competing endogenous RNA (ceRNA) for miR‐219a‑5p, leading to increased expression of the apoptosis inhibitor BIRC3 and thereby promoting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Similarly, studies in colon and prostate cancers reveal that aberrant HCP5 expression supports cellular proliferation and migration via downstream modulation of targets such as AP1G1 and CEMIP and through activation of signaling pathways like PI3K/AKT."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, in osteosarcoma the transcription factor SP1 induces HCP5 overexpression, which facilitates cell growth and epithelial–mesenchymal transition"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while in reproductive disorders such as premature ovarian insufficiency and polycystic ovarian syndrome HCP5 modulates apoptosis and proliferation via interactions with specific microRNAs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the clinical realm, assays based on HCP5 genotyping have been successfully used as surrogate markers for HLA‐B*5701, enabling effective screening to prevent abacavir hypersensitivity reactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Overall, the accumulated evidence indicates that HCP5 operates on two levels: as a genetic marker reflecting favorable immune control of viral infections and as a functional lncRNA that modulates key molecular pathways in tumorigenesis and other pathologic states. These versatile roles render HCP5 a promising biomarker and potential therapeutic target across a broad spectrum of clinical conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sophie Limou, Sigrid Le Clerc, Cédric Coulonges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/596067"}], "href": "https://doi.org/10.1086/596067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19115949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19115949"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cyril Dalmasso, Wassila Carpentier, Laurence Meyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0003907"}], "href": "https://doi.org/10.1371/journal.pone.0003907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19107206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19107206"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daniëlle van Manen, Neeltje A Kootstra, Brigitte Boeser-Nunnink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "AIDS (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAD.0b013e32831db247"}], "href": "https://doi.org/10.1097/QAD.0b013e32831db247"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19050382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19050382"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ying Liu, Cynthia Helms, Wilson Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000041"}], "href": "https://doi.org/10.1371/journal.pgen.1000041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18369459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18369459"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "D R Crosslin, D S Carrell, A Burt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in the HLA region is associated with susceptibility to herpes zoster."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2014.51"}], "href": "https://doi.org/10.1038/gene.2014.51"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25297839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25297839"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Honglei Wu, Bin Liu, Zhaosheng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2426-z"}], "href": "https://doi.org/10.1038/s41419-020-2426-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32300102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32300102"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lihong Wang, Tian Luan, Shunheng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2335"}], "href": "https://doi.org/10.1002/cam4.2335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31215169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31215169"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jing Chen, Dongjing Zhao, Qiang Meng "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of HCP5 exerts tumor-suppressive functions by up-regulating tumor suppressor miR-128-3p in anaplastic thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2019.108966"}], "href": "https://doi.org/10.1016/j.biopha.2019.108966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31102936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31102936"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Renguang Hu, Zhongjie Lu "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA HCP5 promotes prostate cancer cell proliferation by acting as the sponge of miR‑4656 to modulate CEMIP expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2019.7404"}], "href": "https://doi.org/10.3892/or.2019.7404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31746434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31746434"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Weidong Zhao, Li Li "}, {"type": "b", "children": [{"type": "t", "text": "SP1-induced upregulation of long non-coding RNA HCP5 promotes the development of osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2018.12.006"}], "href": "https://doi.org/10.1016/j.prp.2018.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30554864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30554864"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaoyan Wang, Xinyue Zhang, Yujie Dang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkaa127"}], "href": "https://doi.org/10.1093/nar/gkaa127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32112110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32112110"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yongqian Chen, Xiaolei Zhang, Yuan An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HCP5 promotes cell proliferation and inhibits apoptosis via miR-27a-3p/IGF-1 axis in human granulosa-like tumor cell line KGN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2019.110697"}], "href": "https://doi.org/10.1016/j.mce.2019.110697"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31891769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31891769"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sara Colombo, Andri Rauch, Margalida Rotger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/591184"}], "href": "https://doi.org/10.1086/591184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18684101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18684101"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yuanzhang Zou, Binghai Chen "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA HCP5 in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chim Acta (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cca.2020.11.015"}], "href": "https://doi.org/10.1016/j.cca.2020.11.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33245911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33245911"}]}]}]}