{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HHIP‐AS1 is a long noncoding RNA that has emerged as an important regulator in a variety of biological contexts, particularly in cancer and tissue remodeling. In triple‐negative breast cancer cells, HHIP‐AS1 is directly regulated by the TGFβ/SMAD2/3 signaling pathway, as demonstrated by SMAD2/3 binding at its promoter (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hepatocellular carcinoma, its expression is markedly reduced, and lower levels correlate with larger tumor size, metastasis, advanced TNM stage, and worse overall survival. Functionally, HHIP‐AS1 suppresses cell proliferation, migration, and invasion while promoting apoptosis by stabilizing HHIP mRNA via a HuR‐dependent mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In lung cancer, HHIP‐AS1 expression is significantly diminished compared to normal tissue. Its overexpression inhibits epithelial–mesenchymal transition (EMT) and cellular stemness by sponging miR‑153‑3p, thereby modulating the expression of PCDHGA9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in head and neck squamous cell carcinoma, decreased expression of HHIP‐AS1, alongside that of HHIP, is associated with aberrant hedgehog pathway regulation and poorer survival outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its functional roles in cancer progression, HHIP‐AS1 has also been identified as a prognostic biomarker. Its altered expression is included among panels in ovarian cancer prognostic models"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and its downregulation under mechanical compressive forces in periodontal ligament stem cells suggests a role in bone remodeling during orthodontic tooth movement."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that HHIP‐AS1 functions as a context‐dependent regulator. In cancers such as hepatocellular carcinoma, lung cancer, and head and neck squamous cell carcinoma, it acts predominantly as a tumor suppressor by modulating key signaling pathways and maintaining proper regulation of hedgehog and TGFβ signaling. Moreover, its expression levels may serve as valuable prognostic indicators and therapeutic targets in cancer and potentially in regenerative medicine.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Radhakrishnan Vishnubalaji, Nehad M Alajez "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-94514-9"}], "href": "https://doi.org/10.1038/s41598-021-94514-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34326372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34326372"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Changwen Bo, Xiuli Li, Li He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel long noncoding RNA HHIP-AS1 suppresses hepatocellular carcinoma progression through stabilizing HHIP mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.09.137"}], "href": "https://doi.org/10.1016/j.bbrc.2019.09.137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31604528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31604528"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiaxiang Ye, Siyao Wu, Shan Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Risk scoring based on expression of long non‑coding RNAs can effectively predict survival in hepatocellular carcinoma patients with or without fibrosis."}]}, {"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.2020.7528"}], "href": "https://doi.org/10.3892/or.2020.7528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32323856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32323856"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhuanzhuan Zhou, Yanping Lai, Shan Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA HHIP‑AS1 inhibits lung cancer epithelial‑mesenchymal transition and stemness by regulating PCDHGA9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2021.12485"}], "href": "https://doi.org/10.3892/mmr.2021.12485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34643245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34643245"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Balarko Chakraborty, Mukta Basu, Debalina Mukhopadhyay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential promoter usages of PTCH1 and down regulation of HHIP are associated with HNSCC progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2022.153827"}], "href": "https://doi.org/10.1016/j.prp.2022.153827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35276608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35276608"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Na Li, Xianquan Zhan "}, {"type": "b", "children": [{"type": "t", "text": "Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EPMA J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13167-019-00175-0"}], "href": "https://doi.org/10.1007/s13167-019-00175-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31462944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31462944"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qianyi Qin, Haoqing Yang, Chen Zhang, et al. 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