{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genetic association studies and meta‐analyses have indicated that a common single nucleotide polymorphism in the mature sequence of miR‑4293 (rs12220909) is linked to a decreased risk of certain cancers. For example, one investigation in a Chinese population reported that the rs12220909 variant correlates with a 23% reduction in risk for esophageal squamous cell carcinoma, while a separate study demonstrated that this variant is also associated with reduced susceptibility to non‑small cell lung cancer. Complementary meta‑analyses further reinforce the notion that the heterozygous genotype of rs12220909 exerts a protective effect on cancer initiation by potentially modulating gene networks involved in myeloid cell development and transcriptional regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these genetic observations, functional studies have uncovered oncogenic roles for miR‑4293 when its expression is upregulated. In lung carcinoma tissues and cell lines, heightened levels of miR‑4293 promote proliferation and metastasis while inhibiting apoptosis. Mechanistic insights reveal that miR‑4293 directly targets the mRNA‑decapping enzyme DCP2, leading to its suppression, which in turn facilitates an increase in the oncogenic long non‑coding RNA WFDC21P. This cascade suggests that miR‑4293 serves as a key regulator in lung cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, miR‑4293 is also implicated in non‑malignant disease processes. In the context of steroid‑associated osteonecrosis of the femoral head, genome‑wide association studies have identified a susceptibility locus containing miR‑4293. Bioinformatics analyses suggest that miR‑4293 exerts its effects by regulating a PPARG‑related adipogenesis pathway, thereby contributing to disease pathogenesis in patients with systemic lupus erythematosus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ping Zhang, Jianguo Wang, Ting Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3422-2"}], "href": "https://doi.org/10.1007/s13277-015-3422-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26055141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26055141"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lixia Fan, Linqi Chen, Xiaoling Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0175666"}], "href": "https://doi.org/10.1371/journal.pone.0175666"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28410417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28410417"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dan Ji, Mei An, Qiong Fang "}, {"type": "b", "children": [{"type": "t", "text": "Whether miR-4293 rs12220909 variant affects cancer susceptibility: evidence from 11255 subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Artif Cells Nanomed Biotechnol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21691401.2020.1773483"}], "href": "https://doi.org/10.1080/21691401.2020.1773483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32496828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32496828"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rongqiang Liu, Hongyuan Fu, Yajie Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of miR-4293 rs12220909 polymorphism with cancer risk: A meta-analysis of 8394 subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000021364"}], "href": "https://doi.org/10.1097/MD.0000000000021364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32769868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32769868"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qian Zhang, Yun-Fei Yan, Qing Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04021-y"}], "href": "https://doi.org/10.1038/s41419-021-04021-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34301920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34301920"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hiroyuki Suetsugu, Kwangwoo Kim, Takuaki Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddab306"}], "href": "https://doi.org/10.1093/hmg/ddab306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34850884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34850884"}]}]}]}