{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑302d, a member of the miR‑302 family, has emerged as an important regulator of cell proliferation and differentiation in diverse cellular contexts. In human adipose‐derived stem cells, for example, transfection with a miR‑302d mimic enhanced cell proliferation and conferred protection against oxidant‐induced cell death through downregulation of key targets such as CDKN1A and CCL5 (1). In a similar vein, miR‑302d was shown to promote the proliferation of human pluripotent stem cell‐derived cardiomyocytes by directly targeting LATS2 in the Hippo pathway (8), and upregulation of the miR‑302 cluster was observed during in vitro dedifferentiation of human pancreatic islet cells, suggesting a role in maintaining a less mature, more stem‐like state (4)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its pro‐proliferative actions, miR‑302d (and its mature isoform miR‑302d‑3p) has been implicated in modulating differentiation and specialized cell functions. In retinal pigment epithelial (RPE) cells, ectopic expression of miR‑302d‑3p induces dedifferentiation—accompanied by decreased expression of characteristic RPE markers, impaired phagocytosis, and enhanced migration and cell‐cycle progression—through direct targeting of the cyclin‐dependent kinase inhibitor p21Waf1/Cip1 (5, 11). A related role is evident in chondrocytes, where suppression of miR‑302d‑3p increases cell viability, colony formation, and migration while affecting NF‑κB pathway activity via modulation of ULK1 expression (9)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in controlling proliferation and differentiation, miR‑302d influences disease‐specific signaling pathways. In the context of autoimmunity, its expression is decreased in monocytes from systemic lupus erythematosus patients, leading to derepression of interferon regulatory factor‑9 (IRF9) and subsequent overactivation of interferon‐stimulated gene expression (3). In breast cancer, miR‑302d‑3p is downregulated, and its restoration suppresses cell viability and migration by targeting TMBIM6 and thereby inhibiting extracellular signal‑regulated kinase (ERK) signaling (10). In ovarian pathology, miR‑302d is significantly overexpressed in germ cell tumors compared with clear cell carcinomas, underscoring its potential as a diagnostic marker (2). Moreover, under hypoxic conditions in human umbilical vascular endothelial cells, miR‑302d is downregulated; this may relieve inhibition on factors such as LINC01693 and CXCL12, ultimately contributing to angiogenic responses (7). Although less is known about its role in liver cancer stem cells, emerging evidence suggests that members of the miR‑302 family may also participate in regulating stemness in hepatocellular carcinoma (6)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Y Kim, K K Shin, A L Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.344"}], "href": "https://doi.org/10.1038/cddis.2014.344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25144720"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25144720"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fei Xu, Jingcheng Yang, Jun Shang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "LATS2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in the Hippo pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Sci (Lond) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/CS20190099"}], "href": "https://doi.org/10.1042/CS20190099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31239293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31239293"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guido Sebastiani, Giuseppina Emanuela Grieco, Noemi Brusco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA Expression Analysis of In Vitro Dedifferentiated Human Pancreatic Islet Cells Reveals the Activation of the Pluripotency-Related MicroRNA Cluster miR-302s."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms19041170"}], "href": "https://doi.org/10.3390/ijms19041170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29649109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29649109"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chao Jiang, Ping Xie, Ruxu Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "c-Jun-mediated microRNA-302d-3p induces RPE dedifferentiation by targeting p21"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "Waf1/Cip1"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "."}]}, {"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/s41419-018-0481-5"}], "href": "https://doi.org/10.1038/s41419-018-0481-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29670082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29670082"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaonan Hu, Maximilian Binter, Karsten Hufendiek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-302d inhibits TGFB-induced EMT and promotes MET in primary human RPE cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0278158"}], "href": "https://doi.org/10.1371/journal.pone.0278158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36441751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36441751"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shangzeng Wang, Yongzhi Zheng, Zheng Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulated miR‑302d‑3p promotes chondrocyte proliferation and migration by regulation of Unc‑51‑like kinase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2019.4267"}], "href": "https://doi.org/10.3892/ijmm.2019.4267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31524222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31524222"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Siobhán Smith, Thilini Fernando, Pei Wen Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-302d targets IRF9 to regulate the IFN-induced gene expression in SLE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Autoimmun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaut.2017.03.003"}], "href": "https://doi.org/10.1016/j.jaut.2017.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28318807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28318807"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sang-Geun Jang, Chong Woo Yoo, Sang Yoon Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low expression of miR-449 in gynecologic clear cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Gynecol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/IGC.0000000000000267"}], "href": "https://doi.org/10.1097/IGC.0000000000000267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25238166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25238166"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yang Sun, Xiang Xiong, Xiancheng Wang "}, {"type": "b", "children": [{"type": "t", "text": "RELA promotes hypoxia-induced angiogenesis in human umbilical vascular endothelial cells via LINC01693/miR-302d/CXCL12 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.28521"}], "href": "https://doi.org/10.1002/jcb.28521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30937967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30937967"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yanru Liao, Zhenxiong Qiu, Ling Bai "}, {"type": "b", "children": [{"type": "t", "text": "miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2021.12493"}], "href": "https://doi.org/10.3892/mmr.2021.12493"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34651659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34651659"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yu-Shui Ma, Zhong-Wei Lv, Fei Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-302a/d inhibits the self-renewal capability and cell cycle entry of liver cancer stem cells by targeting the E2F7/AKT axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-018-0927-8"}], "href": "https://doi.org/10.1186/s13046-018-0927-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30326936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30326936"}]}]}]}