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Research on the mechanism of DTL in the occurrence and development of cancer
- 1 Shandong University of Science and Technology
- 2 Shandong University of Science and Technology
* Author to whom correspondence should be addressed.
Abstract
DTL (denticleless E3 ubiquitin protein ligase homolog) is an E3 ubiquitin ligase that is highly expressed in a variety of tumors and is closely related to the occurrence and development of tumors. Here, we review the latest progress in DTL regulation in various cancer data, including the mechanisms by which changes in its expression affect multiple pathways, ultimately leading to cell cycle arrest and tumor proliferation. Future research should further elucidate the molecular mechanism of DTL and its relationship with tumorigenesis, which is of great significance for the prevention, diagnosis and treatment of tumors. In addition, multi-omics data need to be used to further explore the differential expression and regulatory network of DTL at the single cell level, which is crucial for finding tumor suppressor drug targets.
Keywords
DTL, Cancer, cell cycle, oncogene, biomarker.
[1]. Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209–249. DOI:10.3322/caac.21660.
[2]. Hanahan D, Weinberg R A. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646–674. DOI:10.1016/j.cell.2011.02.013.
[3]. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy[J]. Nature Reviews Cancer, 2017, 17(2): 93–115. DOI:10.1038/nrc.2016.138.
[4]. Abbas T, Dutta A. CRL4 Cdt2: master coordinator of cell cycle progression and genome stability[J]. Cell Cycle, 2011, 10(2): 241–249. DOI:10.4161/cc.10.2.14530.
[5]. Havens C G, Walter J C. Mechanism of crl4 Cdt2 , a pcna-dependent e3 ubiquitin ligase[J]. Genes & Development, 2011, 25(15): 1568–1582. DOI:10.1101/gad.2068611.
[6]. Sansam C L, Shepard J L, Lai K, et al. DTL/cdt2 is essential for both cdt1 regulation and the early g2/m checkpoint[J]. Genes & Development, 2006, 20(22): 3117–3129. DOI:10.1101/gad. 1482106.
[7]. Kim Y, Starostina N G, Kipreos E T. The crl4 Cdt2 ubiquitin ligase targets the degradation of p21 Cip1 to control replication licensing[J]. Genes & Development, 2008, 22(18): 2507–2519. DOI:10.1101/gad.1703708.
[8]. Abbas T, Shibata E, Park J, et al. CRL4Cdt2 regulates cell proliferation and histone gene expression by targeting pr-set7/set8 for degradation[J]. Molecular Cell, 2010, 40(1): 9–21. DOI:10.1016/j.molcel.2010.09.014.
[9]. Ma T, Hu Y, Guo Y, et al. Human umbilical vein endothelial cells-derived microrna-203-containing extracellular vesicles alleviate non-small-cell lung cancer progression through modulating the dtl/p21 axis[J]. Cancer Gene Therapy, 2022, 29(1): 87–100. DOI:10.1038/s41417-020-00292-3.
[10]. Fan Q, Lu Q, Wang G, et al. Optimizing component formula suppresses lung cancer by blocking dtl-mediated pdcd4 ubiquitination to regulate the mapk/jnk pathway[J]. Journal of Ethnopharmacology, 2022, 299: 115546. DOI:10.1016/j.jep.2022.115546.
[11]. Zhang X, Wang X, Song X, et al. Programmed cell death 4 enhances chemosensitivity of ovarian cancer cells by activating death receptor pathway in vitro and in vivo[J]. Cancer Science, 2010, 101(10): 2163–2170. DOI:10.1111/j.1349-7006.2010.01664.x.
[12]. Cui H, Wang Q, Lei Z, et al. DTL promotes cancer progression by pdcd4 ubiquitin-dependent degradation[J]. Journal of Experimental & Clinical Cancer Research, 2019, 38(1): 350. DOI:10.1186/s13046-019-1358-x.
[13]. Liu S, Gu L, Wu N, et al. Overexpression of dtl enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing rac1-jnk-foxo1 axis[J]. Cell Death & Disease, 2021, 12(10): 929. DOI:10.1038/s41419-021-04179-5.
[14]. Abbas T, Dutta A. P21 in cancer: intricate networks and multiple activities[J]. Nature Reviews Cancer, 2009, 9(6): 400–414. DOI:10.1038/nrc2657.
[15]. Ueki T, Nishidate T, Park J H, et al. Involvement of elevated expression of multiple cell-cycle regulator, dtl/ramp (denticleless/ra-regulated nuclear matrix associated protein), in the growth of breast cancer cells[J]. Oncogene, 2008, 27(43): 5672–5683. DOI:10.1038/onc.2008.186.
[16]. Perez-Peamp J. Ubiquitin-conjugating enzyme e2t (ube2t) and denticleless protein homolog (dtl) are linked to poor outcome in breast and lung cancers[J]. SCIENTIfIC REpOrts, [no date].
[17]. Chen Y-C, Chen I, Huang G-J, et al. Targeting dtl induces cell cycle arrest and senescence and suppresses cell growth and colony formation through tpx2 inhibition in human hepatocellular carcinoma cells[J]. OncoTargets and Therapy, 2018, Volume 11: 1601–1616. DOI:10.2147/OTT.S147453.
[18]. Dong R, Zhang D, Han B, et al. DTL is a novel downstream gene of e2f1 that promotes the progressionof hepatocellular carcinoma[J]. Current Cancer Drug Targets, 2023, 23(10): 817–828. DOI:10.2174/1568009623666230511100246.
[19]. Pan X, Chen S, Ye L, et al. Long non-coding rna dlgap1-as1 modulates the development of non-small-cell lung cancer via the microrna-193a-5p/dtl axis[J]. Laboratory Investigation, 2022, 102(11): 1182–1191. DOI:10.1038/s41374-022-00831-6.
[20]. Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, et al. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting dtl[J]. Carcinogenesis, 2012, 33(4): 732–739. DOI:10.1093/carcin/bgs020.
[21]. Kobayashi H, Komatsu S, Ichikawa D, et al. Overexpression of denticleless e3 ubiquitin protein ligase homolog (dtl) is related to poor outcome in gastric carcinoma[J]. Oncotarget, 2015, 6(34): 36615–36624. DOI:10.18632/oncotarget.5620.
[22]. Luo X, Liu J, Wang X, et al. Circ‐DTL sponges mir‐758‐3p to accelerate cervical cancer malignant progression by regulating dcun1d1 expression[J]. Journal of Biochemical and Molecular Toxicology, 2023, 37(11): e23462. DOI:10.1002/jbt.23462.
[23]. Luo Y, He Z, Liu W, et al. DTL is a prognostic biomarker and promotes bladder cancer progression through regulating the akt/mtor axis[J]. Oxidative Medicine and Cellular Longevity, [no date].
[24]. Lu J-J, Chen F-J, Li Y, et al. DTL promotes melanoma progression through rewiring cell glucose metabolism[J]. Annals of Translational Medicine, 2022, 10(2): 68–68. DOI:10.21037/atm-21-6648.
[25]. Higa L A, Banks D, Wu M, et al. L2DTL/cdt2 interacts with the cul4/ddb1 complex and pcna and regulates cdt1 proteolysis in response to dna damage[J]. Cell Cycle, 2006, 5(15): 1675–1680. DOI:10.4161/cc.5.15.3149.
[26]. Melixetian M, Ballabeni A, Masiero L, et al. Loss of geminin induces rereplication in the presence of functional p53[J]. The Journal of Cell Biology, 2004, 165(4): 473–482. DOI:10.1083/jcb.200403106.
[27]. Tachibana K K, Gonzalez M A, Guarguaglini G, et al. Depletion of licensing inhibitor geminin causes centrosome overduplication and mitotic defects[J]. EMBO Reports, 2005, 6(11): 1052–1057. DOI:10.1038/sj.embor.7400527.
[28]. Gupta I, Collier P G, Haase B, et al. Single-cell isoform rna sequencing characterizes isoforms in thousands of cerebellar cells[J]. Nature Biotechnology, 2018, 36(12): 1197–1202. DOI:10.1038/nbt.4259.
[29]. Svensson V, Vento-Tormo R, Teichmann S A. Exponential scaling of single-cell rna-seq in the past decade[J]. Nature Protocols, 2018, 13(4): 599–604. DOI:10.1038/nprot.2017.149.
[30]. Mereu E, Lafzi A, Moutinho C, et al. Benchmarking single-cell rna-sequencing protocols for cell atlas projects[J]. Nature Biotechnology, 2020, 38(6): 747–755. DOI:10.1038/s41587-020-0469-4.
[31]. Ulianov S V, Razin S V. The two waves in single-cell 3d genomics[J]. Seminars in Cell & Developmental Biology, 2022, 121: 143–152. DOI:10.1016/j.semcdb.2021.05.021.
[32]. Zhou T, Zhang R, Ma J. The 3d genome structure of single cells[J]. Annual Review of Biomedical Data Science, 2021, 4(1): 21–41. DOI:10.1146/annurev-biodatasci-020121-084709.
[33]. Chen K, Wang Q, Li M, et al. Single-cell rna-seq reveals dynamic change in tumor microenvironment during pancreatic ductal adenocarcinoma malignant progression[J]. EBioMedicine, 2021, 66: 103315. DOI:10.1016/j.ebiom.2021.103315.
[34]. Raghavan S, Winter P S, Navia A W, et al. Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer[J]. Cell, 2021, 184(25): 6119-6137.e26. DOI:10.1016/j.cell. 2021.11.017.
[35]. Tikhonova A N, Dolgalev I, Hu H, et al. The bone marrow microenvironment at single-cell resolution[J]. Nature, 2019, 569(7755): 222–228. DOI:10.1038/s41586-019-1104-8.
[36]. Perez-Peña J, Corrales-Sánchez V, Amir E, et al. Ubiquitin-conjugating enzyme e2t (ube2t) and denticleless protein homolog (dtl) are linked to poor outcome in breast and lung cancers[J]. Scientific Reports, 2017, 7(1): 17530. DOI:10.1038/s41598-017-17836-7.
[37]. Werba G, Weissinger D, Kawaler E A, et al. Single-cell rna sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment[J]. Nature Communications, 2023, 14(1): 797. DOI:10.1038/s41467-023-36296-4.
[38]. Liu Z, Chen Y, Xia Q, et al. Linking genome structures to functions by simultaneous single-cell hi-c and rna-seq: 6649[J]. Science, 2023, 380(6649): 1070–1076. DOI:10.1126/science. adg3797.
[39]. Yousuf S, Qiu M, Voith Von Voithenberg L, et al. Spatially resolved multi-omics single-cell analyses inform mechanisms of immune dysfunction in pancreatic cancer[J]. Gastroenterology, 2023, 165(4): 891-908.e14. DOI:10.1053/j.gastro.2023.05.036.
Cite this article
Yue,S.;Fang,Y. (2024). Research on the mechanism of DTL in the occurrence and development of cancer. Theoretical and Natural Science,49,53-59.
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The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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Volume title: Proceedings of the 4th International Conference on Biological Engineering and Medical Science
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