{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-4651 functions as a tumor‐suppressive microRNA in several cancer types. In non‐small cell lung cancer, it directly binds to the 3′‐UTR of the oncogene BRD4, downregulating its expression and subsequently inhibiting cell proliferation, migration, and tumor growth in vitro and in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hepatocellular carcinoma, reduced miR-4651 levels correlate with elevated FOXP4 expression, and forced overexpression of miR-4651 suppresses cell proliferation while promoting apoptosis by directly targeting FOXP4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn nasopharyngeal carcinoma, a competitive endogenous RNA network has been identified in which the long noncoding RNA HOXC-AS1 sequesters miR-4651. This sponging effect relieves miR-4651-mediated repression of FOXO6, resulting in enhanced FOXO6 expression that contributes to increased cell proliferation, migration, and invasion, thereby promoting cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, miR-4651 regulates RNA quality control by modulating nonsense-mediated mRNA decay. It achieves this by targeting SMG9, a critical component of the NMD pathway; suppression of SMG9 leads to reduced NMD activity and a subsequent increase in the levels of its substrate genes, including TBL2 and GADD45B."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jiangnan Zheng, Yan Zhang, Shang Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-4651 targets bromodomain-containing protein 4 to inhibit non-small cell lung cancer cell progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2020.02.018"}], "href": "https://doi.org/10.1016/j.canlet.2020.02.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32081805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32081805"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yun Li, Xiaoying Wang, Zhonggang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-4651 represses hepatocellular carcinoma cell growth and facilitates apoptosis via targeting FOXP4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20194011"}], "href": "https://doi.org/10.1042/BSR20194011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32436934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32436934"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhiyuan Tang, Xianhai Zeng, Juanjuan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXC-AS1 promotes nasopharyngeal carcinoma (NPC) progression by sponging miR-4651 and subsequently upregulating FOXO6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jphs.2021.08.002"}], "href": "https://doi.org/10.1016/j.jphs.2021.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34507637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34507637"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanjie Tan, Zhenfa Ma, Yi Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA 4651 regulates nonsense-mediated mRNA decay by targeting SMG9 mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2019.03.031"}], "href": "https://doi.org/10.1016/j.gene.2019.03.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30902786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30902786"}]}]}]}