{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAccumulating evidence from multiple studies demonstrates that miR‑379 (and its mature isoform miR‑379‑5p) functions as a potent tumor suppressor in diverse cancer types. In breast, hepatocellular, bladder, cervical, and lung cancers as well as diffuse gliomas and glioma, reduced miR‑379 expression has been associated with increased cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT) and more aggressive clinical stages. For example, in breast cancer lower miR‑379 expression correlates with elevated Cyclin B1 levels and higher tumor stage, while in hepatocellular carcinoma its restoration inhibits cell migration and invasion by repressing focal adhesion kinase and downstream AKT signaling. Similarly, in bladder and cervical cancers, downregulation of miR‑379 permits increased expression of oncogenic targets that drive disease progression, and in non‑small cell lung cancer (NSCLC) its decreased levels have been linked with chemoresistance and unchecked cell growth through dysregulation of proliferation‐promoting factors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have revealed that miR‑379 exerts its tumor‐suppressive effects by directly targeting multiple pro‑oncogenic mRNAs. In breast cancer, miR‑379 lowers COX‑2 and Cyclin B1 levels, whereas in hepatocellular carcinoma and gastric cancer it targets focal adhesion kinase (FAK) and GRB10 to suppress AKT‐driven signaling pathways. In glioblastoma, sequestration of miR‑379‑5p by the circular RNA circ‑PITX1 de‑represses MAP3K2 expression, promoting tumor progression. Additional mechanisms include direct targeting of CHUK in NSCLC, inhibition of TCF‑4 in laryngeal carcinoma, and suppression of CRKL in cervical cancer. Moreover, miR‑379 activity is modulated by non‑coding RNAs—such as lncRNA LINC00665 and specific circular RNAs—that act as molecular sponges, thereby influencing chemoresistance (for instance, through IGF1 regulation) and other oncogenic processes. Altogether, these findings underscore a multilayered regulatory network in which miR‑379 normally restrains key effectors of cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_fs", "start_ref": "6", "end_ref": "8"}, {"type": "fg_fs", "start_ref": "13", "end_ref": "15"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in tumor suppression, miR‑379 influences several physiological and disease‐related processes by modulating gene networks involved in metabolism, inflammation, and cellular stress responses. In metabolic contexts, glucocorticoid‑induced miR‑379 affects hepatic lipid handling, and epigenetic studies have linked its expression to key regulators of retinoic acid signaling. In the ovary, aberrant miR‑379‑5p expression impairs granulosa cell proliferation and DNA repair—contributing to premature ovarian insufficiency—and, in polycystic ovarian syndrome (PCOS), androgen‑stimulated exosomal release of miR‑379‑5p has been shown to influence granulosa cell fate and local inflammatory responses. Additionally, altered miR‑379 levels are associated with intestinal barrier dysfunction during ischemia–reperfusion injury, further emphasizing its multifaceted role in regulating cellular homeostasis. Collectively, these findings highlight the potential of miR‑379 (and the larger miR‑379/miR‑656 cluster) as both a diagnostic biomarker and a therapeutic target across a wide spectrum of human diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "19"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "20"}, {"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sonja Khan, Cathy L Brougham, James Ryan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-379 regulates cyclin B1 expression and is decreased in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0068753"}], "href": "https://doi.org/10.1371/journal.pone.0068753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23874748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23874748"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jing-Song Chen, Hua-Shu Li, Jiong-Qiang Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2016.02.043"}], "href": "https://doi.org/10.1016/j.canlet.2016.02.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26944318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26944318"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guang-Jun Hao, Hai-Jun Hao, Yan-Hui Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.12566"}], "href": "https://doi.org/10.1002/1873-3468.12566"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28117895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28117895"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Deyao Wu, Xiaobing Niu, Jun Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5607"}], "href": "https://doi.org/10.3892/or.2017.5607"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28498468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28498468"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meizhong Xu, Shui Qin, Fan Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-379 inhibits metastasis and epithelial-mesenchymal transition via targeting FAK/AKT signaling in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2017.4072"}], "href": "https://doi.org/10.3892/ijo.2017.4072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28713929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28713929"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "K P O'Brien, S Khan, K E Gilligan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-017-0116-9"}], "href": "https://doi.org/10.1038/s41388-017-0116-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29367765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29367765"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Subhashree Nayak, Meghali Aich, Anupam Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-26000-8"}], "href": "https://doi.org/10.1038/s41598-018-26000-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29769662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29769662"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bin Liu, Zheng Wang, Shizhao Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR‑379 inhibits cell proliferation and epithelial‑mesenchymal transition by targeting CHUK through the NF‑κB pathway in non‑small cell lung cancer."}]}, {"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.2019.10362"}], "href": "https://doi.org/10.3892/mmr.2019.10362"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31173238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31173238"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yonghong Jiang, Panpan Zhu, Yamei Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR‑379‑5p inhibits cell proliferation and promotes cell apoptosis in non‑small cell lung cancer by targeting β‑arrestin‑1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.11553"}], "href": "https://doi.org/10.3892/mmr.2020.11553"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33173959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33173959"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Baoyi Yang, Shitao Xia, Xiangmei Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-379-5p targets microsomal glutathione transferase 1 (MGST1) to regulate human glioma in cell proliferation, migration and invasion and epithelial-mesenchymal transition (EMT)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.05.099"}], "href": "https://doi.org/10.1016/j.bbrc.2021.05.099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34171541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34171541"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Li-Li Ren, Zhi-Wen Wang, Ren Sen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GRB10 is a novel factor associated with gastric cancer proliferation and prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.204603"}], "href": "https://doi.org/10.18632/aging.204603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37179120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37179120"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Roldan M de Guia, Adam J Rose, Anke Sommerfeld, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-379 couples glucocorticoid hormones to dysfunctional lipid homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201490464"}], "href": "https://doi.org/10.15252/embj.201490464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25510864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25510864"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jin-Long Wei, Liang Zhang, Zhi-Ming Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-379 inhibits laryngeal carcinoma cell proliferation and invasion through directly targeting TCF-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kaohsiung J Med Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/kjm2.12109"}], "href": "https://doi.org/10.1002/kjm2.12109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31436384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31436384"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Xinwen Lv, Meihua Wang, Jingli Qiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2019.172643"}], "href": "https://doi.org/10.1016/j.ejphar.2019.172643"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31493405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31493405"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Reza Salehi, Meshach Asare-Werehene, Brandon A Wyse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2023.1104550"}], "href": "https://doi.org/10.3389/fimmu.2023.1104550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37033997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37033997"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Lifei Wang, Dongchang Wang, Zhen Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circ_0010235 confers cisplatin resistance in lung cancer by upregulating E2F7 through absorbing miR-379-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thorac Cancer (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1759-7714.14941"}], "href": "https://doi.org/10.1111/1759-7714.14941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37277864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37277864"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Zirui Jia, Yuhang Wang, Jiacheng Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-379-5P INHIBITION ENHANCES INTESTINAL EPITHELIAL PROLIFERATION AND BARRIER FUNCTION RECOVERY AFTER ISCHEMIA/REPERFUSION BY TARGETING EIF4G2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Shock (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/SHK.0000000000002205"}], "href": "https://doi.org/10.1097/SHK.0000000000002205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37646610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37646610"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sriharikrishnaa Srinath, Padacherri Vethil Jishnu, Vinay Koshy Varghese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.13611"}], "href": "https://doi.org/10.1002/1878-0261.13611"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38400534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38400534"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yujie Dang, Xiaoyan Wang, Yajing Hao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency through PARP1 and XRCC6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-017-0163-8"}], "href": "https://doi.org/10.1038/s41419-017-0163-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29367615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29367615"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Wei Ji, Yu-Ling Diao, Yi-Ran Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B 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/s41419-019-2213-x"}], "href": "https://doi.org/10.1038/s41419-019-2213-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31907362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31907362"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Shine-Gwo Shiah, Jenn-Ren Hsiao, Hsiao-Ju Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biomed Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12929-020-00644-z"}], "href": "https://doi.org/10.1186/s12929-020-00644-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32238162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32238162"}]}]}]}