{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐190A is emerging as a context‐dependent regulator in cancer progression. In several studies, its expression has been shown to modulate key oncogenic pathways: for example, trivalent arsenic (As³⁺) induced miR‐190 expression in bronchial epithelial cells, which in turn downregulated negative regulators of Akt signaling, thereby promoting proliferation and malignant transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In breast cancer, increased miR‐190A expression was associated with inhibition of cell migration and invasiveness through direct targeting of metastasis‐promoting proteins such as protease‐activated receptor‑1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and a similar metastasis‐suppressive role was observed being linked to estrogen receptor signaling. In prostate cancer, miR‐190A is an integral component of an auto‐regulatory loop with androgen receptor (AR) and YB‑1, in which miR‑190A downregulation correlates with enhanced AR signaling and poorer clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, miR‐190A has been shown to silence long non‐coding targets such as treRNA in hepatoma cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and in glioma models, its binding by lncRNA PVT1 modulated the expression of the oncogene MEF2C."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Conversely, stable overexpression of miR‑190 in hepatocellular carcinoma decreased the expression of the tumor suppressor PHLPP1 and thereby enhanced AKT activation to promote proliferation and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In cervical cancer models, viral oncoproteins were found to downregulate miR‑190A"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while in additional breast cancer studies, miR‑190 was implicated in suppressing epithelial–mesenchymal transition (EMT) and angiogenesis by targeting stanniocalcin‑2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and further experiments confirmed that miR‑190 overexpression can inhibit EMT and angiogenesis via the AKT‑ERK pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, analysis in Wilms’ tumor alludes to a role for miR‐190 family members, although the precise molecular mechanism remains to be clarified."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its varied effects on proliferation and metastasis, miR‑190A exerts control over the tumor microenvironment. Its ability to modulate angiogenic effectors has been demonstrated by direct targeting of several factors that regulate vascular endothelial growth factor (VEGF) expression, thereby contributing to the suppression of tumor angiogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Moreover, upregulation of miR‑190 was identified as a consistent feature in dormant tumors, suggesting that it may induce or maintain a prolonged dormant state through extensive transcriptional reprogramming.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside the classical oncologic arena, miR‑190A holds promise as both a functional mediator in non‐cancerous processes and as a potential biomarker. In the context of viral infections, Epstein–Barr virus latency is accompanied by marked upregulation of miR‑190, which enhances host cell survival via targeting TP53INP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In pulmonary vascular diseases, reviews have highlighted roles for miR‑190—as well as other miRNAs—in the development of pulmonary arterial hypertension"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", and clinical studies have shown that circulating miR‑190 levels change dynamically with hypoxia, correlating with increased pulmonary artery pressures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": " Furthermore, in gestational diabetes mellitus, miR‑190B appears to influence pancreatic β‑cell proliferation and insulin secretion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", while in cases of pulmonary thromboembolism, plasma levels of miR‑190 may offer diagnostic value."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Finally, in cervical cancer, the miR‑190A–KLF6 axis has been implicated in tumor progression, and in pre‑eclampsia, a miR‑190A/DAPK1 pathway modulates trophoblast autophagy, highlighting its diverse regulatory roles in non‐malignant disease states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kevin Beezhold, Jia Liu, Hong Kan, et al. 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