{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMRPL58, also known as immature colon carcinoma transcript‐1 (ICT1), is an integral component of the large subunit of the human mitochondrial ribosome. Unlike other mitochondrial translation release factors that are matrix‐soluble, ICT1 is embedded within the mitoribosome where it retains ribosome‐dependent peptidyl‐tRNA hydrolase activity without codon specificity. This unique activity is critical for releasing stalled nascent chains by hydrolyzing prematurely terminated peptidyl–tRNA molecules, thereby preserving mitochondrial protein synthesis and ensuring cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in mitochondrial translation, ICT1 exhibits prominent oncogenic properties across a variety of human cancers. Elevated ICT1 expression has been documented in colorectal cancer, non‐small cell lung cancer, breast cancer, diffuse large B-cell lymphoma, gastric cancer, hepatocellular carcinoma, osteosarcoma, and leukemia. Functional studies demonstrate that ICT1 overexpression promotes cell proliferation by facilitating cell cycle progression—often through upregulation of cyclins and cyclin-dependent kinases—and by inhibiting apoptosis via increased levels of anti-apoptotic proteins such as Bcl-2, while ICT1 depletion leads to cell cycle arrest (at G0/G1 or G2/M phases) and activation of apoptotic cascades. Moreover, its expression is regulated by specific microRNAs (e.g., miR-205 and miR-134) and linked to signaling axes such as STAT3/BCL-2, underscoring its potential as both a prognostic biomarker and a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings reveal that MRPL58/ICT1 plays a dual role in cellular homeostasis: it is essential for maintaining mitochondrial translation fidelity while concurrently modulating key regulators of cell proliferation and apoptosis to drive tumorigenesis. This multifaceted role highlights ICT1’s potential as a molecular target for the development of novel diagnostic and therapeutic strategies in cancer treatment.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ricarda Richter, Joanna Rorbach, Aleksandra Pajak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.14"}], "href": "https://doi.org/10.1038/emboj.2010.14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20186120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20186120"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xinyuan Lao, Qingyang Feng, Guodong He, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ICT1 knockdown inhibits breast cancer cell growth via induction of cell cycle arrest and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2017.2913"}], "href": "https://doi.org/10.3892/ijmm.2017.2913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28290601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28290601"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wenjun Xie, Meijuan Wu, Tianhong Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ICT1 predicts a poor survival and correlated with cell proliferation in diffuse large B-cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2017.06.028"}], "href": "https://doi.org/10.1016/j.gene.2017.06.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28629825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28629825"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Youmao Tao, Yan Song, Tao Han, et al. 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