{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent research has characterized LDL receptor‐related protein 9 (LRP9) as a unique transmembrane receptor that does not localize to the plasma membrane but instead cycles between the trans‐Golgi network and endosomal compartments. This intracellular trafficking is governed by critical acidic cluster/dileucine motifs that mediate binding to clathrin adaptor GGA proteins, underscoring a novel mechanism of receptor sorting and signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a complementary study, the calcium‐binding protein Calnuc was found to interact with LRP9 via its arginine‐rich cytosolic domain. Calnuc’s interaction is essential for maintaining proper LRP9 localization, as its depletion results in mistargeting of LRP9 to late endosomal/lysosomal compartments and enhanced degradation. This finding emphasizes the intricate regulation of receptor trafficking by accessory proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these studies on receptor trafficking, recent data have revealed a pivotal role for miR‐1538 in colorectal cancer (CRC). Expression of miR‐1538 is significantly down‐regulated in CRC tissues and cell lines, with its reduced levels correlating with larger tumor size, advanced clinical stage, and poorer prognosis. Functional studies demonstrated that miR‑1538 exerts tumor-suppressive effects by directly targeting the 3′‑UTR of DNMT3A mRNA, thereby decreasing DNMT3A protein levels. This downregulation leads to inhibition of cancer cell proliferation, migration, and invasion, suggesting that miR‑1538 may serve as an important prognostic biomarker and potential therapeutic target in CRC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rémi Boucher, Heidi Larkin, Julie Brodeur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intracellular trafficking of LRP9 is dependent on two acidic cluster/dileucine motifs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-008-0436-5"}], "href": "https://doi.org/10.1007/s00418-008-0436-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18461348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18461348"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Julie Brodeur, Heidi Larkin, Rémi Boucher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calnuc binds to LRP9 and affects its endosomal sorting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2009.00933.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2009.00933.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19497050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19497050"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaodong Zhang, Yi Yang, Weiguang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of MiR-1538 promotes proliferation and metastasis of colorectal cancer by targeting DNMT3A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.04.006"}], "href": "https://doi.org/10.1016/j.bbrc.2022.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35429679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35429679"}]}]}]}