{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA GHET1 is emerging as a critical oncogenic regulator implicated in the progression of a wide spectrum of human cancers. Elevated GHET1 expression has been reported in gastric, colorectal, bladder, hepatocellular, esophageal, non‐small cell lung, ovarian, osteosarcoma, cervical, pancreatic, triple‐negative breast, thyroid, and prostate cancers, and its high levels are strongly associated with increased tumor size, advanced clinical stage, lymph node and distant metastases, chemoresistance, and ultimately poor overall survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, in gastric carcinoma GHET1 binds to IGF2BP1 to enhance the stability of c‐Myc mRNA and promote cell‐cycle progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", while in colorectal and bladder cancers it stimulates proliferation, invasion, and epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In hepatocellular carcinoma, GHET1 represses tumor‐suppressive factors such as KLF2, and in esophageal squamous cell carcinoma it is associated with aggressive, metastatic phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in non‐small cell lung and cervical cancers GHET1 modulates key signaling cascades—including the LATS1/YAP and PTEN/PI3K/AKT pathways—to facilitate cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In ovarian cancer, GHET1 promotes metabolic reprogramming by interacting with von Hippel–Lindau protein to block HIF1α degradation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and in bladder as well as gastric cancers its overexpression contributes to chemoresistance through upregulation of drug efflux transporters and anti‐apoptotic factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Similarly, in pancreatic, osteosarcoma, triple‐negative breast, thyroid, and prostate cancers, GHET1 enhances cell cycle progression and inhibits apoptosis via modulation of multiple oncogenic pathways—including Wnt/β‐catenin, Notch, and downstream effectors such as c‐Myc."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": " In breast cancer, for instance, GHET1 has been shown to drive progression by modulating epidermal growth factor receptor signaling and its downstream PI3K/AKT cascade"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and in colon cancer its expression is enhanced by PITX2, which in turn promotes activation of the Wnt/β-catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, several meta‐analyses have consolidated these findings, demonstrating that high GHET1 expression is significantly correlated with adverse clinicopathological features and unfavorable patient outcomes across various tumor types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "21"}]}, {"type": "t", "text": " Additional studies in triple‐negative breast cancer have further shown that GHET1 can activate the Hippo/YAP pathway in response to hypoxia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that GHET1 functions as a multifunctional oncogene by engaging in diverse molecular processes—ranging from stabilization of oncogenic transcripts and modulation of cell cycle regulators to activation of multiple pro‐tumorigenic signaling pathways. Consequently, GHET1 holds promise as both a diagnostic biomarker and a therapeutic target in a range of human malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Feng Yang, Xuchao Xue, Luming Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.12625"}], "href": "https://doi.org/10.1111/febs.12625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24397586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24397586"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jianyu Zhou, Xiaorong Li, Meirong Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of Long Noncoding RNA GHET1 Inhibits Cell Proliferation and Invasion of Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504016X14567549091305"}], "href": "https://doi.org/10.3727/096504016X14567549091305"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27131316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27131316"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lin-Jin Li, Jian-Long Zhu, Wen-Shuo Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA GHET1 promotes the development of bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2014)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25400817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25400817"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Li Jin, Yangke He, Shijia Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GHET1 predicts poor prognosis in hepatocellular carcinoma and promotes cell proliferation by silencing KLF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.26257"}], "href": "https://doi.org/10.1002/jcp.26257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29139562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29139562"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongfen Liu, Qiang Zhen, Yakun Fan "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GHET1 promotes esophageal squamous cell carcinoma cells proliferation and invasion via induction of EMT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Markers (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5301/ijbm.5000304"}], "href": "https://doi.org/10.5301/ijbm.5000304"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28983895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28983895"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhen-Biao Guan, Yu-Shu Cao, Yi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of lncRNA GHET1 suppresses cell proliferation, invasion and LATS1/YAP pathway in non small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biomark (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/CBM-170431"}], "href": "https://doi.org/10.3233/CBM-170431"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29286919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29286919"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wang Ling, Xu Yangchun, Wang Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of long non-coding RNA GHET1 suppresses cervical carcinoma in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biomark (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/CBM-190269"}], "href": "https://doi.org/10.3233/CBM-190269"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32176622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32176622"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dan Liu, Hao Li "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA GEHT1 promoted the proliferation of ovarian cancer cells via modulating the protein stability of HIF1α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20181650"}], "href": "https://doi.org/10.1042/BSR20181650"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30988076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30988076"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bo Li, Dalon Xie, Hui Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA GHET1 contributes to chemotherapeutic resistance to Gemcitabine in bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-019-03873-8"}], "href": "https://doi.org/10.1007/s00280-019-03873-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31115606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31115606"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xianwen Zhang, Ping Bo, Liang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of long non-coding RNA GHET1 promotes the development of multidrug resistance in gastric cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2017.04.111"}], "href": "https://doi.org/10.1016/j.biopha.2017.04.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28578256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28578256"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "H-Y Zhou, H Zhu, X-Y Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and clinical significance of long-non-coding RNA GHET1 in pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201711_13822"}], "href": "https://doi.org/10.26355/eurrev_201711_13822"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29228419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29228419"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xingli Chen, Wei Zhao, Weimin Fan "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA GHET1 promotes osteosarcoma development and progression via Wnt/β‑catenin signaling pathway."}]}, {"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.2020.7585"}], "href": "https://doi.org/10.3892/or.2020.7585"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32319657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32319657"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yu Wang, Chen Li "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA GHET1 Promotes the Progression of Triple-Negative Breast Cancer "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "via"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Regulation of miR-377-3p/GRSF1 Signaling Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comput Math Methods Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/8366569"}], "href": "https://doi.org/10.1155/2022/8366569"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35509860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35509860"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yan Liu, Ping Shi, Hao Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA GHET1 promotes thyroid cancer cell proliferation and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21037/tcr-21-1615"}], "href": "https://doi.org/10.21037/tcr-21-1615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35116711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35116711"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yanfeng Zhu, Yue Tong, Jianhua Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF-1α/Notch-1 signaling pathway via KLF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biofactors (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/biof.1486"}], "href": "https://doi.org/10.1002/biof.1486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30609158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30609158"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Mingli Han, Yimeng Wang, Yuanting Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA GHET1 knockdown suppresses breast cancer activity in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Transl Res (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30787968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30787968"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yang He, Peng Gong, Sitong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The significance of homeodomain transcription factor 2 in colon cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Eng Online (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12938-021-00912-5"}], "href": "https://doi.org/10.1186/s12938-021-00912-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34372865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34372865"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jing Ye, Haiyan Sun, Zhengquan Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic significance of LncRNA GHET1 expression in various cancers: a systematic review and meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20190608"}], "href": "https://doi.org/10.1042/BSR20190608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31227613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31227613"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yao-Fei Jiang, Hong-Yan Zhang, Jin Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of LncRNA GHET1 predicts an unfavourable survival and clinical parameters of patients in various cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.14486"}], "href": "https://doi.org/10.1111/jcmm.14486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31251476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31251476"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Arash Poursheikhani, Negin Nokhandani, Hassan Yousefi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathological Significance of Long Non-Coding RNA GHET1 in Human Cancers: A Meta-Analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Pharm Biotechnol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1389201021999200727163238"}], "href": "https://doi.org/10.2174/1389201021999200727163238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32720600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32720600"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Hua Wang, Fanyu Meng, Surong Dong "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant Expression of Gastric Carcinoma High Expressed Transcript 1 is a Diagnostic and Prognostic Biomarker in Human Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Med Assoc (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jnma.2020.05.017"}], "href": "https://doi.org/10.1016/j.jnma.2020.05.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32653201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32653201"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Yu Wang, Shuwei Liu "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GHET1 Promotes Hypoxia-Induced Glycolysis, Proliferation, and Invasion in Triple-Negative Breast Cancer Through the Hippo/YAP Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2021.643515"}], "href": "https://doi.org/10.3389/fcell.2021.643515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33869194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33869194"}]}]}]}