{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00458, which encodes the long non‐coding RNA “ES3”, has been implicated in cell type–specific regulatory networks. In vascular smooth muscle cells, LINC00458/lncRNA‐ES3 is transcriptionally regulated by the basic helix–loop–helix transcription factor Bhlhe40, and its upregulation under high‐glucose conditions promotes calcification and cellular senescence. Mechanistically, it functions as a competing endogenous RNA that sponges multiple microRNAs (including miR‑95‑5p, miR‑6776‑5p, miR‑3620‑5p, and miR‑4747‑5p) to modulate downstream targets that favor vascular pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, LINC00458/lncRNA‑ES3 has been shown to be significantly upregulated in breast cancer, particularly in high‐grade, high‐stage, and HER2‑positive tumors. Its expression correlates with oncogenic signaling downstream of HER2, while it decreases during neural differentiation, suggesting that LINC00458 participates in maintaining a proliferative, less differentiated state in tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, LINC00458/lncRNA‑ES3 exacerbates vascular calcification and senescence by acting as a competing endogenous RNA for miR‑34c‑5p, thereby enhancing the expression of pro‐senescence factors such as BMF. This regulatory axis further supports its role in vascular pathology under diabetic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Overall, these findings indicate that LINC00458/lncRNA‑ES3 functions as a context‐dependent regulator, contributing to vascular calcification/senescence and breast cancer proliferation through modulation of specific microRNA networks.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jia-Yu Zhong, Xing-Jun Cui, Jun-Kun Zhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA-ES3 inhibition by Bhlhe40 is involved in high glucose-induced calcification/senescence of vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nyas.14381"}], "href": "https://doi.org/10.1111/nyas.14381"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32483833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32483833"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mostafa Keshavarz, Malek Hossein Asadi, Ali Riahi-Madvar "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of pluripotent long noncoding RNA ES3 in HER2-positive breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29152"}], "href": "https://doi.org/10.1002/jcb.29152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31211468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31211468"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiao Lin, Jun-Kun Zhan, Jia-Yu Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs."}]}, {"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.101758"}], "href": "https://doi.org/10.18632/aging.101758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30654331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30654331"}]}]}]}