{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐671, particularly its −5p (and in one study −3p) isoform, has emerged as a multifunctional regulator that modulates gene expression via direct cleavage or translational repression. For example, miR‐671 directs Ago2‐dependent cleavage of a circular antisense transcript at the CDR1 locus, thereby affecting CDR1 mRNA levels and exemplifying one mechanism by which this miRNA regulates non‐coding RNA targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several cancer models, miR‐671 functions as a tumor suppressor. In breast cancer, overexpression of miR‐671‐5p decreases levels of the oncogenic transcription factor FOXM1, reverses epithelial–mesenchymal transition (EMT) toward a more differentiated state, and sensitizes cells to chemotherapeutics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, hypoxia downregulates miR‐671‐5p, leading to upregulation of TUFT1 and consequent activation of the Ca2⁺/PI3K/AKT pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in non–small cell lung cancer, upregulation of miR‐671‐3p restrains cell proliferation and invasion via targeting CCND2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In osteosarcoma, low levels of miR‐671‐5p correlate with increased expression of cell‐cycle promoters such as CCND1, CDC34, and TUFT1, resulting in enhanced tumor cell proliferation, whereas restoration of miR‐671‐5p suppresses these processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Additionally, in malignant melanoma, therapeutic interventions that elevate miR‐671‐5p levels reduce cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, miR‐671 can also exert oncogenic effects in certain tumor types. In glioblastoma multiforme, miR‐671‐5p is overexpressed and promotes migration—and to a lesser extent proliferation—by targeting transcripts such as CDR1‐AS, CDR1, and VSNL1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In soft tissue sarcomas, elevated levels of miR‐671‐5p contribute to the silencing of the tumor suppressor SMARCB1, while in prostate cancer, miR‐671 targets SOX6 and suppresses the expression of NFIA, with consequent effects on CRYAB expression, thereby enhancing cell proliferation and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its direct regulatory activities, miR‐671 is subject to modulation by and interaction with other non‐coding RNAs. In osteosarcoma, the long non‐coding RNA DLEU1 acts as a molecular sponge to sequester miR‐671‐5p, thereby relieving repression of downstream targets such as DDX5. Similarly, in osteoarthritis, the circular RNA circ_0114876 binds miR‐671, modulating TRAF2 expression and affecting chondrocyte viability and inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas B Hansen, Erik D Wiklund, Jesper B Bramsen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-019-1173-5"}], "href": "https://doi.org/10.1186/s13058-019-1173-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31391072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31391072"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Changwei Dou, Zhenyu Zhou, Qiuran Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia-induced TUFT1 promotes the growth and metastasis of hepatocellular carcinoma by activating the Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "/PI3K/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-018-0505-8"}], "href": "https://doi.org/10.1038/s41388-018-0505-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30250300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30250300"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuanshan Yao, Yinjie Zhou, Xiaojun Fu "}, {"type": "b", "children": [{"type": "t", "text": "miR‑671‑3p is downregulated in non‑small cell lung cancer and inhibits cancer progression by directly targeting CCND2."}]}, {"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.2019.9858"}], "href": "https://doi.org/10.3892/mmr.2019.9858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30664171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30664171"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chaofei Xin, Shitao Lu, Yu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-671-5p Inhibits Tumor Proliferation by Blocking Cell Cycle in Osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2019.4870"}], "href": "https://doi.org/10.1089/dna.2019.4870"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31393166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31393166"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Cao Ma, Zhi-Kui Nie, Hong-Min Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-671-5p plays a promising role in restraining osteosarcoma cell characteristics through targeting TUFT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem Mol Toxicol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbt.22490"}], "href": "https://doi.org/10.1002/jbt.22490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32115852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32115852"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bo Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Guizhi Fuling pills inhibit the proliferation, migration and invasion of human cutaneous malignant melanoma cells by regulating the molecular axis of LncRNA TPT1-AS1 / miR-671-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol (Noisy-le-grand) (2020)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33040829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33040829"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Davide Barbagallo, Angelo Condorelli, Marco Ragusa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6621"}], "href": "https://doi.org/10.18632/oncotarget.6621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26683098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26683098"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zoltán Sápi, Gergő Papp, Miklós Szendrői, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic regulation of SMARCB1 By miR-206, -381 and -671-5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR-765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.22379"}], "href": "https://doi.org/10.1002/gcc.22379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27223121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27223121"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yin Yu, Zhixin Wang, Daju Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-671 promotes prostate cancer cell proliferation by targeting tumor suppressor SOX6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2018.01.016"}], "href": "https://doi.org/10.1016/j.ejphar.2018.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29355560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29355560"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "X G Chi, X X Meng, D L Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2019_190217N135"}], "href": "https://doi.org/10.4149/neo_2019_190217N135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31686521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31686521"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zhiguo Zhu, Lianmin Luo, Qian Xiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiRNA-671-5p Promotes prostate cancer development and metastasis by targeting NFIA/CRYAB axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03138-w"}], "href": "https://doi.org/10.1038/s41419-020-03138-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33144585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33144585"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Xinxin Chen, Chengyong Zhang, Xiao Wang "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Artif Cells Nanomed Biotechnol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21691401.2019.1648285"}], "href": "https://doi.org/10.1080/21691401.2019.1648285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31379208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31379208"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Qiushi Wang, Simin Luo, Jie Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circ_0114876 promoted IL-1β-induced chondrocyte injury by targeting miR-671/TRAF2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biotechnol Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10529-020-03070-1"}], "href": "https://doi.org/10.1007/s10529-020-03070-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33404903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33404903"}]}]}]}