{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐940 (miR-940) plays multifaceted roles in cancer biology that appear to be highly context dependent. In certain malignancies, such as nasopharyngeal carcinoma, hepatocellular carcinoma, glioma, and triple-negative breast cancer, reduced intracellular levels of miR-940 correlate with aggressive tumor behavior and poor prognosis. For instance, in hepatocellular carcinoma, restoration of miR-940 expression has been reported to inhibit cell proliferation and invasion through targeting molecules like ESRRG and SPOCK1, while in glioma, miR-940 promotes oncogenic effects via downregulation of KLF9. In contrast, in other settings—such as gastric cancer, pancreatic carcinoma, and endometrial carcinoma—overexpression of miR-940 contributes to enhanced proliferation, migration, and invasion by modulating key signaling pathways (e.g., via repression of ZNF24, activation of Wnt/β-catenin signaling through targeting GSK3β/sFRP1, or by regulating PD-L1 expression). Moreover, studies have demonstrated the utility of miR-940 as a minimally invasive biomarker; for example, its altered levels in saliva and plasma have been proposed for the early detection of pancreatic and gastric cancers, and its serum level is under investigation in breast cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, miR-940 is involved in several non-neoplastic processes. During cardiac development, for example, markedly decreased miR-940 expression in the right ventricular outflow tract has been associated with aberrant proliferation and migration of cardiomyocyte progenitors—findings that may relate to congenital heart defects such as Tetralogy of Fallot. In reproductive biology, miR-940 has been implicated in the regulation of placental implantation, suggesting that its dysregulation could contribute to early abortion. Additionally, in osteoarthritis, reduced miR-940 levels lead to enhanced inflammation, likely via derepression of the adaptor molecule MyD88 involved in NF-κB signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn ovarian cancer, miR-940 appears to have dual and seemingly paradoxical functions. On one hand, intracellular miR-940 acts as a tumor suppressor by targeting oncogenic mediators such as the proto-oncogene SRC, thereby inhibiting cell proliferation, migration, and invasion. On the other hand, under hypoxic conditions, ovarian cancer cells secrete miR-940 enriched exosomes that are taken up by tumor-associated macrophages; this exosomal miR-940 promotes M2 polarization, which in turn supports tumor proliferation and migration. These contrasting roles underscore the complexity of miR-940’s impact on the tumor microenvironment and cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Ma, F Sun, C Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2016.06.057"}], "href": "https://doi.org/10.1016/j.biopha.2016.06.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27459115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27459115"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lingmi Hou, Maoshan Chen, Hongwei Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinical potential of miR-940 as a diagnostic and prognostic biomarker in breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biomark (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/CBM-171124"}], "href": "https://doi.org/10.3233/CBM-171124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29843213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29843213"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "G-M Gu, Y-Y Zhan, K Abuduwaili, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA‑940 promotes cell proliferation and invasion of glioma by directly targeting Kruppel‑like factor 9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2018.9630"}], "href": "https://doi.org/10.3892/mmr.2018.9630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30431124"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30431124"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Peng Li, Zhiwei Xiao, Jiajun Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-139-5p, miR-940 and miR-193a-5p inhibit the growth of hepatocellular carcinoma by targeting SPOCK1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.14121"}], "href": "https://doi.org/10.1111/jcmm.14121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30710422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30710422"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Zhan Zhou, Ya-Ping Xu, Li-Juan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-940 potentially promotes proliferation and metastasis of endometrial carcinoma through regulation of MRVI1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20190077"}], "href": "https://doi.org/10.1042/BSR20190077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31085718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31085718"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Huayao Zhang, Jingwen Peng, Jianguo Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-940 promotes malignant progression of breast cancer by regulating FOXO3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20201337"}], "href": "https://doi.org/10.1042/BSR20201337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32840296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32840296"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Dandan Liang, Xinran Xu, Fangfei Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNA-940 reduction contributes to human Tetralogy of Fallot development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12309"}], "href": "https://doi.org/10.1111/jcmm.12309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24889693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24889693"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "C-Y Zhang, X-L Lu, Y Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Highly expressed microRNA-940 promotes early abortion by regulating placenta implantation by targeting ZNF672."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201904_17539"}], "href": "https://doi.org/10.26355/eurrev_201904_17539"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31002163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31002163"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jian Cao, Zhongxing Liu, Limin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-940 regulates the inflammatory response of chondrocytes by targeting MyD88 in osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-019-03601-z"}], "href": "https://doi.org/10.1007/s11010-019-03601-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31435813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31435813"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Mohammed H Rashed, Pinar Kanlikilicer, Cristian Rodriguez-Aguayo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15525"}], "href": "https://doi.org/10.18632/oncotarget.15525"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28423620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28423620"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Xin Chen, Xiang Ying, Xinjing Wang, et al. 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