{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMKLN1‐AS, a long non‐coding RNA, is markedly upregulated in hepatocellular carcinoma (HCC) and is significantly associated with poor clinical outcomes, including shortened overall and disease‐free survival, vascular invasion, and an aggressive tumor phenotype. Functionally, MKLN1‐AS operates as a competing endogenous RNA (ceRNA) by sponging key tumor‐suppressive microRNAs. In one mechanism, it sequesters miR‑654‑3p to increase the expression of hepatoma‑derived growth factor (HDGF), thereby promoting cell proliferation, migration, invasion, and evasion of apoptosis. In another regulatory circuit, MKLN1‐AS binds to miR‑22‑3p leading to the upregulation of the oncogenic transcription factor ETS1. These studies collectively underscore the potential prognostic value of MKLN1‐AS as well as its promise as a therapeutic target in HCC."}, {"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 addition, the transcription factor SOX9 has been shown to directly bind to the promoter of MKLN1‐AS, significantly upregulating its expression in HCC cells. This upregulation further enhances cell viability, proliferation, invasion, and epithelial–mesenchymal transition, thereby fueling the malignant progression of HCC and emphasizing the pivotal role of MKLN1‐AS in mediating SOX9‐driven oncogenic processes."}, {"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 involvement in HCC, MKLN1‐AS also plays a crucial role in the progression of pancreatic ductal adenocarcinoma (PDAC). Under hypoxic conditions, hypoxia‑inducible factor‑1α (HIF‑1α) directly binds to a hypoxia response element within the MKLN1‑AS promoter, thereby inducing its expression. Once upregulated, MKLN1‑AS acts as a ceRNA by sponging miR‑185‑5p, which leads to increased expression of TEAD1 and ultimately promotes PDAC cell proliferation, migration, and tumor growth. These findings suggest that the MKLN1‑AS axis may serve as a promising therapeutic target and prognostic indicator not only in HCC but also in hypoxia‐driven malignancies such as PDAC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wanjun Gao, Xiaohua Chen, Wei Chi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2020.4722"}], "href": "https://doi.org/10.3892/ijmm.2020.4722"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33000222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33000222"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chao Guo, Shuhuang Zhou, Weimin Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) is a potential diagnostic and prognostic biomarker and therapeutic target for hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Pathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexmp.2021.104638"}], "href": "https://doi.org/10.1016/j.yexmp.2021.104638"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33878313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33878313"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guozheng Pan, Jian Zhang, Faping You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ETS Proto-Oncogene 1-activated muskelin 1 antisense RNA drives the malignant progression of hepatocellular carcinoma by targeting miR-22-3p to upregulate ETS Proto-Oncogene 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.2017565"}], "href": "https://doi.org/10.1080/21655979.2021.2017565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34983308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34983308"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xijun Chen, Qing Ye, Zhigao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA muskelin 1 antisense RNA as a potential therapeutic target in hepatocellular carcinoma treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2074703"}], "href": "https://doi.org/10.1080/21655979.2022.2074703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35579449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35579449"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chao Guo, Shuhuang Zhou, Weimin Yi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX9/MKLN1-AS Axis Induces Hepatocellular Carcinoma Proliferation and Epithelial-Mesenchymal Transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10528-022-10196-6"}], "href": "https://doi.org/10.1007/s10528-022-10196-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35138470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35138470"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jiayu Chen, Lei Li, Yongpu Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Toxicol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10565-024-09863-8"}], "href": "https://doi.org/10.1007/s10565-024-09863-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38740637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38740637"}]}]}]}