{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IDH1‐AS1 is a long noncoding RNA that has emerged as a context‐dependent regulator of cancer cell metabolism and proliferation. In prostate cancer, IDH1‐AS1 is upregulated via activation by transcription factors such as PAX5, and it promotes tumor growth by enhancing autophagy. Mechanistically, it stabilizes the mRNA of ATG5—either through direct post‐transcriptional regulation or by sequestering specific microRNAs like miR‐216b‐5p—resulting in increased autophagy that supports cell proliferation and survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, in glioma, IDH1‐AS1 is downregulated, and its forced overexpression impedes cell cycle progression and cell proliferation while promoting apoptosis. Notably, although IDH1‐AS1 does not change IDH1 protein levels in glioma cells, it modifies the enzyme’s activity, suggesting that its tumor‐suppressive effects may be mediated through alterations in cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Further highlighting its role in metabolic regulation, studies have demonstrated that under normoxic conditions the oncogene c‐Myc transcriptionally represses IDH1‐AS1. When expressed, IDH1‐AS1 promotes the homodimerization of IDH1, leading to enhanced enzymatic activity, increased production of α‐ketoglutarate, reduced reactive oxygen species, and subsequent downregulation of HIF1α. This cascade results in attenuation of glycolysis (the Warburg effect) and suppression of cell proliferation, establishing IDH1‐AS1 as a potential metabolic checkpoint in tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that IDH1‐AS1 functions as a dual‐edged regulator in cancer: it promotes tumor growth in prostate cancer by stimulating autophagy, whereas in glioma and in the context of c‐Myc–mediated metabolic regulation, its expression appears to limit tumor progression. As such, IDH1‐AS1 may serve not only as a biomarker but also as a promising therapeutic target for modulating cancer metabolism and growth.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nan Zhang, Zhongyi Li, Fuding Bai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX5-induced upregulation of IDH1-AS1 promotes tumor growth in prostate cancer by regulating ATG5-mediated autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-019-1932-3"}], "href": "https://doi.org/10.1038/s41419-019-1932-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31570703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31570703"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shuo Wu, Liucheng Ding, Hewei Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Long Non-Coding RNA "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "IDH1-AS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Promotes Prostate Cancer Progression by Enhancing IDH1 Enzyme Activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S251915"}], "href": "https://doi.org/10.2147/OTT.S251915"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32884284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32884284"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jubo Wang, Yu Quan, Jian Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/bcb-2019-0465"}], "href": "https://doi.org/10.1139/bcb-2019-0465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32990028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32990028"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shaoxun Xiang, Hao Gu, Lei Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1711257115"}], "href": "https://doi.org/10.1073/pnas.1711257115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29378948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29378948"}]}]}]}