{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCirculating miR‐652 has emerged as a promising non‐invasive biomarker for early disease detection. In breast cancer, for example, elevated levels of miR‐652 in plasma were found in both benign tumors and early‐stage malignancies, suggesting its potential use in diagnosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In non‐small cell lung cancer, miR‐652 (often analyzed in combination with other miRNAs such as miR‐660) was significantly upregulated in patient serum, thereby improving diagnostic accuracy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in patients with acute decompensated heart failure the circulating level of miR‐652‑3p was shown to aid in the early diagnosis of acute kidney injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and in rectal cancer, its expression correlated with radiotherapy response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn tumor cells miR‐652 appears to play context‐dependent roles. In pancreatic cancer, an acidic microenvironment suppressed miR‐652 expression, which in turn released the inhibition on ZEB1 to promote epithelial–mesenchymal transition (EMT)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " By contrast, in non‐small cell lung cancer tissues miR‐652‑3p was notably increased, where functional experiments showed that it promoted proliferation, migration, and invasion by directly targeting tumor suppressors such as Lgl1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In pediatric acute lymphoblastic leukemia, lower miR‐652‑3p levels at diagnosis that were subsequently restored in complete remission suggested a tumor‐suppressive role and an influence on chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Similar investigations in gastric"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", bladder"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and endometrial carcinomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "have underscored its prognostic value. In uveal melanoma, overexpression of miR‐652 promoted cell proliferation and migration by targeting HOXA9 and activating HIF‐1α signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In ovarian cancer, interactions between circRNA_MYLK and miR‐652 are implicated in malignant progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma elevated levels of miR‐652‑3p, both in tissue and in exosomes derived from bone marrow‐mesenchymal stem cells, correlated with advanced stage and enhanced metastatic capabilities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, miR‐652 is involved in several non‐malignant cellular and systemic processes. Within the immune compartment, reviews of myeloid cell miRNA profiles have identified miR‐652 as an important regulator in monocytes, neutrophils, eosinophils, basophils, and mast cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Its upregulation in blood from high‐risk individuals for bipolar disorder points to a role in neuropsychiatric susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Moreover, overexpression of miR‐652‑3p in adipocytes has been linked to enhanced insulin‐stimulated lipogenesis, while in macrophages its regulatory function appears central to lipid metabolism and inflammatory cytokine secretion in atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Finally, in the placental context, decreased levels of miR‐652‑3p in preeclamptic tissues and its modulation of crucial regulators such as HOXA9 and EphB4 or associated with sumoylation factors have been linked to impaired trophoblast function and reduced placental growth factor production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katarina Cuk, Manuela Zucknick, Dharanija Madhavan, et al. 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