{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LACTB, a mitochondrial serine protease, has emerged as a pivotal regulator linking mitochondrial lipid metabolism to cell differentiation and tumor suppression. In breast cancer cells, LACTB inhibits proliferation and promotes differentiation by altering mitochondrial lipid pathways—specifically through the reduction of phosphatidylserine decarboxylase levels, which in turn impairs phosphatidylethanolamine synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colorectal cancer and glioma, epigenetic downregulation of LACTB is associated with metastasis, advanced clinical stages, and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in melanoma, LACTB overexpression suppresses cell proliferation, migration, and invasion by modulating key oncogenic pathways such as YAP via enhanced phosphorylation, thereby blocking its nuclear translocation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its tumor‐suppressive role, LACTB is involved in normal physiological processes. During skeletal myogenesis, LACTB is directly targeted by miR‐351-5p and indirectly regulated by the lncRNA lnc-mg, which together modulate muscle cell proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the context of atherosclerosis, miR‐125b-5p downregulates LACTB, leading to decreased expression of the chemokine MCP-1 and reflecting an anti-inflammatory mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have further revealed that LACTB assembles into higher-order filamentous structures essential for its proteolytic activity. These analyses also underscore the existence of multiple splicing isoforms in different cell types, such as leukemic cell lines, suggesting an additional layer of functional diversity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in breast cancer, aberrant regulation of LACTB by miR-374a contributes to enhanced tumorigenicity, further supporting its role as a critical tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings emphasize that LACTB functions as a key modulator of mitochondrial lipid metabolism and cell differentiation, acting as a tumor suppressor in multiple cancer types and participating in normal tissue homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zuzana Keckesova, Joana Liu Donaher, Jasmine De Cock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LACTB is a tumour suppressor that modulates lipid metabolism and cell state."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21408"}], "href": "https://doi.org/10.1038/nature21408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28329758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28329758"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kaixuan Zeng, Xiaoxiang Chen, Xiuxiu Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LACTB, a novel epigenetic silenced tumor suppressor, inhibits colorectal cancer progression by attenuating MDM2-mediated p53 ubiquitination and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-018-0352-7"}], "href": "https://doi.org/10.1038/s41388-018-0352-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29899406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29899406"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hai-Tao Li, Dao-Yong Dong, Qiang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of LACTB, a Mitochondrial Protein That Inhibits Proliferation and Invasion in Glioma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504017X15030178624579"}], "href": "https://doi.org/10.3727/096504017X15030178624579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28835318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28835318"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yawen Ma, Lihua Wang, Fanglin He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LACTB suppresses melanoma progression by attenuating PP1A and YAP interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.02.022"}], "href": "https://doi.org/10.1016/j.canlet.2021.02.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33675985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33675985"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jingjing Du, Peiwen Zhang, Xue Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase-β and is regulated by lnc-mg."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201701394RRR"}], "href": "https://doi.org/10.1096/fj.201701394RRR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30216112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30216112"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jing-Bo Lu, Xing-Xing Yao, Jian-Cheng Xiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2015.11.007"}], "href": "https://doi.org/10.1016/j.abb.2015.11.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26603571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26603571"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Minghui Zhang, Laixing Zhang, Runyu Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the catalytic activity of filamentous human serine beta-lactamase-like protein LACTB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2022.02.007"}], "href": "https://doi.org/10.1016/j.str.2022.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35247327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35247327"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ze-Ying Liu, Fang Yang, Wei Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Alternative Splicing Analysis of LACTB Gene and Expression Characteristics of Different Transcripts in Leukemia Cell Lines]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Shi Yan Xue Ye Xue Za Zhi (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.19746/j.cnki.issn.1009-2137.2021.04.002"}], "href": "https://doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34362477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34362477"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun Zhang, Yuting He, Yan Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.1576"}], "href": "https://doi.org/10.1002/cam4.1576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29790671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29790671"}]}]}]}