{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FLJ39080, also known as MIR2052HG, is a long noncoding RNA that plays a critical regulatory role in estrogen receptor–positive breast cancer. It exerts its function primarily by interacting with the transcription factor EGR1, which it helps recruit to the promoter of LMTK3. The ensuing increase in LMTK3 expression contributes to the maintenance of estrogen receptor‐α (ERα) levels through a dual mechanism: firstly, by promoting AKT/FOXO3‐mediated transcription of the ESR1 gene; and secondly, by limiting ubiquitin‐mediated, proteasome‐dependent degradation of ERα via suppression of protein kinase C (PKC) activity and its downstream MEK/ERK/RSK1 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genome‐wide analyses have further revealed that genetic polymorphisms within FLJ39080/MIR2052HG are functionally significant. Variant alleles modulate MIR2052HG expression in response to hormonal stimuli and aromatase inhibitor therapy, resulting in altered ERα binding dynamics and, ultimately, influencing both breast cancer recurrence risk and responses to endocrine treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Additionally, reviews have underscored its emerging role in aromatase‐dependent cancers via transcriptional regulation of aromatase (CYP19A1) and modulation of estrogen synthesis, further linking FLJ39080/MIR2052HG to tumor progression and treatment outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, investigations into the association of MIR2052HG genetic variants with conditions such as recurrent miscarriage have not established a significant correlation, suggesting that its critical functional impact is more closely aligned with the regulation of estrogen signaling in breast cancer rather than other reproductive pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, FLJ39080/MIR2052HG emerges as a pivotal modulator of ERα stability and estrogen signaling, offering a potential target for therapeutic intervention in ERα‐positive breast cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junmei Cairns, James N Ingle, Krishna R Kalari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lncRNA MIR2052HG regulates ERα levels and aromatase inhibitor resistance through LMTK3 by recruiting EGR1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-019-1130-3"}], "href": "https://doi.org/10.1186/s13058-019-1130-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30944027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30944027"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James N Ingle, Fang Xie, Matthew J Ellis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Polymorphisms in the Long Noncoding RNA MIR2052HG Offer a Pharmacogenomic Basis for the Response of Breast Cancer Patients to Aromatase Inhibitor Therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-16-1371"}], "href": "https://doi.org/10.1158/0008-5472.CAN-16-1371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27758888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27758888"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tushar Singh Barwal, Uttam Sharma, Sonali Bazala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs and Long Noncoding RNAs as Novel Therapeutic Targets in Estrogen Receptor-Positive Breast and Ovarian Cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22084072"}], "href": "https://doi.org/10.3390/ijms22084072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33920789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33920789"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hanran Mai, Canhong Cai, Kun Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between the rs3802201 polymorphism of the lncRNA MIR2052HG gene and the risk of recurrent miscarriage in a Southern Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.24167"}], "href": "https://doi.org/10.1002/jcla.24167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34910326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34910326"}]}]}]}