{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GRAMD1B is a member of the GRAMD1 family of endoplasmic reticulum–anchored proteins that play a critical role in non‐vesicular sterol transfer and cellular cholesterol homeostasis. Studies have shown that GRAMD1B interacts with Niemann–Pick C1 protein at endocytic and ER membrane contact sites to facilitate the direct transfer of cholesterol from late endocytic organelles to the ER."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its conserved GRAM domain acts as a sensor for “accessible” cholesterol as well as anionic lipids such as phosphatidylserine, thereby regulating membrane tethering and defining the rate of cholesterol transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in lipid trafficking, GRAMD1B has been implicated in multiple disease settings. A circular RNA originating from the GRAMD1B gene (circGRAMD1B) functions as an anti‐oncogene in gastric cancer by sponging miR‑130a‑3p and restoring tumor suppressors like PTEN and p21."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In breast cancer cells, decreased GRAMD1B expression is associated with enhanced cell migration through deregulation of the JAK/STAT and Akt pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while genome‐wide association studies have linked variants near GRAMD1B with an increased risk of chronic lymphocytic leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, GRAMD1B is a target of microRNAs that modulate chemotherapeutic response; for instance, miR‑193b* inhibition of GRAMD1B expression contributes to platinum resistance in ovarian cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Its expression in fetal Leydig cells suggests a potential role in steroidogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and genetic association studies in livestock have identified GRAMD1B as a candidate gene linked to reproductive traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight that GRAMD1B is a multifunctional protein central not only to maintaining cholesterol equilibrium via ER–membrane contacts but also to modulating oncogenic signaling and chemotherapeutic responses, thereby influencing tumor biology and potentially other physiological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D Höglinger, T Burgoyne, E Sanchez-Heras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-12152-2"}], "href": "https://doi.org/10.1038/s41467-019-12152-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31537798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31537798"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bilge Ercan, Tomoki Naito, Dylan Hong Zheng Koh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2020106524"}], "href": "https://doi.org/10.15252/embj.2020106524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33604931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33604931"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xinglong Dai, Xiong Guo, Jianjun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA circGRAMD1B inhibits gastric cancer progression by sponging miR-130a-3p and regulating PTEN and p21 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.102414"}], "href": "https://doi.org/10.18632/aging.102414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31719211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31719211"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Puja Khanna, Joan Shuying Lee, Amornpun Sereemaspun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-27864-6"}], "href": "https://doi.org/10.1038/s41598-018-27864-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29934528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29934528"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Susan L Slager, Lynn R Goldin, Sara S Strom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic susceptibility variants for chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-09-1217"}], "href": "https://doi.org/10.1158/1055-9965.EPI-09-1217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20332261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20332261"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dana Ziliak, Eric R Gamazon, Bonnie Lacroix, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation that predicts platinum sensitivity reveals the role of miR-193b* in chemotherapeutic susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-12-0221"}], "href": "https://doi.org/10.1158/1535-7163.MCT-12-0221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22752226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22752226"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sherry Y Wu, Xianbin Yang, Kshipra M Gharpure, et al. "}, {"type": "b", "children": [{"type": "t", "text": "2'-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms4459"}], "href": "https://doi.org/10.1038/ncomms4459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24619206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24619206"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Erin N McDowell, Anne E Kisielewski, Jack W Pike, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0047359"}], "href": "https://doi.org/10.1371/journal.pone.0047359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23133512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23133512"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zitao Chen, Shaopan Ye, Jinyan Teng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association studies for the number of animals born alive and dead in duroc pigs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theriogenology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.theriogenology.2019.07.013"}], "href": "https://doi.org/10.1016/j.theriogenology.2019.07.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31362194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31362194"}]}]}]}