{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR-517a, a member of the C19MC cluster, plays key tumor‐suppressive roles in various cancers. In bladder cancer cells, restoration of miR-517a significantly inhibited cell proliferation and induced apoptosis via modulation of targets such as AREG and BCLAF1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, ectopic expression of miR-517a (and its isoforms) blocked the G2/M transition, thereby reducing cell proliferation through regulation of Pyk2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, studies in lung cancer indicate that miR-517a-3p modulates cell proliferation and invasion, further supporting its tumor-suppressor function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of pregnancy, miR-517a is predominantly expressed in placental trophoblasts and serves as a pivotal modulator of placental function. Exosomal transfer of miR-517a-3p from trophoblast cells to maternal immune cells results in the suppression of target genes such as PRKG1, highlighting a role in placenta–maternal communication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In preeclampsia, upregulation of miR-517a along with its family members was associated with reduced trophoblast invasion and increased production of the anti-angiogenic factor sFLT1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while additional findings implicate roles for miR-517-5p in the pathology of preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Dysregulation of miR-517a has also been linked to gestational metabolic complications; in cases of diabetic macrosomia, reduced miR-517a levels (modulated partly by lncRNA-SNX17) were associated with increased IGF-1 expression, which promoted trophoblast proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, altered expression of miR-517a is featured in placental pathologies such as complete hydatidiform mole"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and placenta previa, where its circulating levels are used to assess placental status."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMiR-517a also exerts potent antiviral effects. Mechanistically, its direct targeting of UNC13D leads to modulation of autophagy, an action that contributes to the suppression of viral replication in recipient cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " This antiviral activity is further supported by findings demonstrating that miR-517a-3p can inhibit human cytomegalovirus replication and reduce viral protein expression in both fibroblasts and trophoblasts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, genomic rearrangements affecting chromosomal band 19q13.4 in thyroid adenomas result in the upregulation of the entire C19MC cluster, implying that aberrant activation of miR-517a may contribute to the pathogenesis of these benign epithelial tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takayuki Yoshitomi, Kazumori Kawakami, Hideki Enokida, et al. 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