{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted the importance of secreted enzymes such as PM20D1 in regulating energy balance, metabolism, and even neuronal function. For example, PM20D1 has been shown to catalyze the formation of bioactive N‑acyl amino acids that serve as endogenous uncouplers, thus promoting energy expenditure and improving glucose homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, perturbations in pathways regulated by PM20D1 have been implicated in obesity and neurophysiological deficits, further underscoring the enzyme’s multifaceted role in metabolic and neural tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel with these metabolic investigations, high-throughput profiling in papillary renal cell carcinoma (PRCC) has identified specific microRNAs with prognostic significance. Among 105 differentially expressed miRNAs, hsa‐mir‑3199‑2 emerged as one of two critical candidates (alongside hsa‐mir‑1293) as determined by LASSO regression analysis. This study predicted that hsa‑mir‑3199‑2 regulates a network of approximately 197 target genes, with functional enrichment in pathways such as the platelet activating factor biosynthetic process, epithelial cell maturation, and the regulation of the IκB kinase complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlthough the mechanistic details of hsa‑mir‑3199‑2’s function remain to be fully elucidated, its differential expression and association with distinct cellular pathways suggest that it may play a regulatory role in PRCC pathogenesis. The integration of these findings with broader insights into metabolic regulation—particularly those involving PM20D1—raises the intriguing possibility that hsa‑mir‑3199‑2 could modulate cancer-relevant processes such as inflammation, cellular maturation, and energy signaling. Ultimately, this positions hsa‑mir‑3199‑2 as a promising prognostic biomarker that may offer novel insights for clinical diagnosis and targeted therapy in PRCC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jonathan Z Long, Katrin J Svensson, Leslie A Bateman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.05.071"}], "href": "https://doi.org/10.1016/j.cell.2016.05.071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27374330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27374330"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jonathan Z Long, Alexander M Roche, Charles A Berdan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of PM20D1 reveals "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "N"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-acyl amino acid control of metabolism and nociception."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1803389115"}], "href": "https://doi.org/10.1073/pnas.1803389115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29967167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29967167"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dandan Li, Yang Liu, Wei Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of miR-324-5p increases PM20D1-mediated white and brown adipose loss and reduces body weight in juvenile mice."}]}, {"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.2019.172708"}], "href": "https://doi.org/10.1016/j.ejphar.2019.172708"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31568785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31568785"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nanshan Song, Yinquan Fang, Hong Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kir6.2 is essential to maintain neurite features by modulating PM20D1-reduced mitochondrial ATP generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2021.102168"}], "href": "https://doi.org/10.1016/j.redox.2021.102168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34673451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34673451"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wen Luo, Lei Wang, Mao-Hua Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hsa-mir-3199-2 and hsa-mir-1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.26008"}], "href": "https://doi.org/10.1002/jcb.26008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28338236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28338236"}]}]}]}