MicroRNAs and the DNA damage response: How is cell fate determined?

DNA Repair - Tập 108 - Trang 103245 - 2021
Hartwig Visser1, Adam D. Thomas1
1Centre for Research in Biosciences, University of the West of England, Frenchay Campus, Bristol BS16 1QY, United Kingdom

Tài liệu tham khảo

Vermeulen, 2003, The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer: Cell cycle regulation and deregulation, Cell Prolif., 36, 131, 10.1046/j.1365-2184.2003.00266.x Visconti, 2016, Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword, J. Exp. Clin. Cancer Res., 35, 153, 10.1186/s13046-016-0433-9 Li, 2008, Homologous recombination in DNA repair and DNA damage tolerance, Cell Res., 18, 99, 10.1038/cr.2008.1 Trenner, 2019, Harnessing DNA double-strand break repair for cancer treatment, Front. Oncol., 9, 1388, 10.3389/fonc.2019.01388 Matt, 2016, The DNA damage-induced cell death response: a roadmap to kill cancer cells, Cell. Mol. Life Sci., 73, 2829, 10.1007/s00018-016-2130-4 Roos, 2016, DNA damage and the balance between survival and death in cancer biology, Nat. Rev. Cancer, 16, 20, 10.1038/nrc.2015.2 Cui, 2016, Radiation induces autophagic cell death via the p53/DRAM signaling pathway in breast cancer cells, Oncol. Rep., 35, 3639, 10.3892/or.2016.4752 Thomas, 2020, Biological basis for threshold responses to methylating agents, Chem. Res. Toxicol., 33, 2219, 10.1021/acs.chemrestox.0c00052 Harton, 2019, p53 pulse modulation differentially regulates target gene promoters to regulate cell fate decisions, Mol. Syst. Biol., 15, 8685, 10.15252/msb.20188685 Mayo, 2005, Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified, J. Biol. Chem., 280, 25953, 10.1074/jbc.M503026200 Ling, 2013, MicroRNAs and other non-coding RNAs as targets for anticancer drug development, Nat. Rev. Drug Discov., 12, 847, 10.1038/nrd4140 Wang, 2013, MicroRNAs and DNA damage response: implications for cancer therapy, Cell Cycle, 12, 32, 10.4161/cc.23051 Malakoti, 2021, The cross-talk between signaling pathways, noncoding RNAs and DNA damage response: emerging players in cancer progression, DNA Repair, 98, 10.1016/j.dnarep.2020.103036 Wang, 2013, Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition, Cell Death Dis., 4, 699, 10.1038/cddis.2013.227 Pothof, 2009, MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response, EMBO J., 28, 2090, 10.1038/emboj.2009.156 Rana, 2020, Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase, Sci. Rep., 10, 5581, 10.1038/s41598-020-62621-8 Syed, 2018, The MRE11–RAD50–NBS1 complex conducts the orchestration of damage signaling and outcomes to stress in DNA replication and repair, Annu. Rev. Biochem., 87, 263, 10.1146/annurev-biochem-062917-012415 Menolfi, 2020, ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion, Cell Biosci., 10, 8, 10.1186/s13578-020-0376-x Bartek, 2003, Chk1 and Chk2 kinases in checkpoint control and cancer, Cancer Cell, 3, 421, 10.1016/S1535-6108(03)00110-7 Stiff, 2004, ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation, Cancer Res., 64, 2390, 10.1158/0008-5472.CAN-03-3207 Wu, 2008, MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks, Proc. Natl. Acad. Sci., 105, 11200, 10.1073/pnas.0802885105 Hirao, 2000, DNA damage-induced activation of p53 by the checkpoint kinase Chk2, Science, 287, 1824, 10.1126/science.287.5459.1824 S.-Y. Shieh, J. Ahn, K. Tamai, Y. Taya, & C. Prives, The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. 12. Zhang, 2014, Roles of Chk1 in cell biology and cancer therapy, Int. J. Cancer, 134, 1013, 10.1002/ijc.28226 Canman, 1998, Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53, Science, 281, 1677, 10.1126/science.281.5383.1677 Nakagawa, 1999, Requirement of ATM in Phosphorylation of the Human p53 Protein at Serine 15 following DNA Double-Strand Breaks, Mol. Cell. Biol., 19, 2828, 10.1128/MCB.19.4.2828 Tibbetts, 1999, A role for ATR in the DNA damage-induced phosphorylation of p53, Genes Dev., 13, 152, 10.1101/gad.13.2.152 Saito, 2002, ATM mediates phosphorylation at multiple p53 sites, including ser 46, in response to ionizing radiation, J. Biol. Chem., 277, 12491, 10.1074/jbc.C200093200 Lu, 2007, The Wip1 Phosphatase Acts as a Gatekeeper in the p53-Mdm2 Autoregulatory Loop, Cancer Cell, 12, 342, 10.1016/j.ccr.2007.08.033 Lu, 2008, The Wip1 phosphatase and Mdm2: Cracking the ‘Wip’ on p53 stability, Cell Cycle, 7, 164, 10.4161/cc.7.2.5299 Shreeram, 2006, Wip1 phosphatase modulates ATM-dependent signaling pathways, Mol. Cell, 23, 757, 10.1016/j.molcel.2006.07.010 Freeman, 2010, Phosphatases in the cellular response to DNA damage, Cell Commun. Signal., 8, 27, 10.1186/1478-811X-8-27 Macurek, 2013, Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis, Cell Cycle, 12, 251, 10.4161/cc.23057 Jabbur, 2000, DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo, Oncogene, 19, 6203, 10.1038/sj.onc.1204017 Loughery, 2014, Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters, Nucleic Acids Res., 42, 7666, 10.1093/nar/gku501 Smeenk, 2011, Role of p53 Serine 46 in p53 Target Gene Regulation, PLoS One, 6, 10.1371/journal.pone.0017574 Oda, 2000, p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by ser-46-phosphorylated p53, Cell, 102, 849, 10.1016/S0092-8674(00)00073-8 Feng, 2006, Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence, Cell Cycle, 5, 2812, 10.4161/cc.5.23.3526 He, 2019, The SIAH1–HIPK2–p53ser46 damage response pathway is involved in temozolomide-induced glioblastoma cell death, Mol. Cancer Res., 17, 1129, 10.1158/1541-7786.MCR-18-1306 Winter, 2008, Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR, Nat. Cell Biol., 10, 812, 10.1038/ncb1743 Tang, 2008, Acetylation is indispensable for p53 activation, Cell, 133, 612, 10.1016/j.cell.2008.03.025 Yun, 2016, Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway, J. Biol. Chem., 291, 7386, 10.1074/jbc.M115.706341 Jiang, 2010, Decision making by p53: life versus death, Mol. Cell. Pharmacol., 16 Yang, 2015, Acetylation of HDAC1 and degradation of SIRT1 form a positive feedback loop to regulate p53 acetylation during heat-shock stress, Cell Death Dis., 6, 1747, 10.1038/cddis.2015.106 Ren, 2019, The role of different SIRT1-mediated signaling pathways in toxic injury, Cell. Mol. Biol. Lett., 24, 36, 10.1186/s11658-019-0158-9 Bouras, 2005, SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1, J. Biol. Chem., 280, 10264, 10.1074/jbc.M408748200 Conrad, 2016, HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism, Cell Death Differ, 23, 110, 10.1038/cdd.2015.75 Zannini, L., Buscemi, G., Kim, J.-E., Fontanella, E. & Delia, D. DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage. 10. Hu, 2011, MicroRNAs: new players in the DNA damage response, J. Mol. Cell Biol, 3, 151, 10.1093/jmcb/mjq042 Lee, 2004, MicroRNA genes are transcribed by RNA polymerase II, EMBO J., 23, 4051, 10.1038/sj.emboj.7600385 Denli, 2004, Processing of primary microRNAs by the Microprocessor complex, Nature, 432, 231, 10.1038/nature03049 Feng, 2011, Tumor suppressor p53 meets microRNAs, J. Mol. Cell Biol., 3, 44, 10.1093/jmcb/mjq040 Majidinia, 2020, MicroRNAs, DNA damage response and ageing, Biogerontology, 21, 275, 10.1007/s10522-020-09862-2 Pratt, 2009, The RNA-induced silencing complex: a versatile gene-silencing machine, J. Biol. Chem., 284, 17897, 10.1074/jbc.R900012200 Hermeking, 2012, MicroRNAs in the p53 network: micromanagement of tumour suppression, Nat. Rev. Cancer, 12, 613, 10.1038/nrc3318 Höck, 2008, The Argonaute protein family, Genome Biol., 9, 210, 10.1186/gb-2008-9-2-210 Zhang, 2011, The ATM Kinase Induces MicroRNA Biogenesis in the DNA Damage Response, Mol. Cell, 41, 371, 10.1016/j.molcel.2011.01.020 Trabucchi, 2009, The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs, Nature, 459, 1010, 10.1038/nature08025 Cortez, 1999, Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks, Science, 286, 1162, 10.1126/science.286.5442.1162 Kawai, 2012, BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex, J. Cell Biol, 197, 201, 10.1083/jcb.201110008 Gatei, M. et al. Role for ATM in DNA Damage-induced Phosphorylation of BRCA1. 7. Martin, 2013, ATM–Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response, PLoS Genet., 9, 10.1371/journal.pgen.1003505 Zou, 2003, Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes, Science, 300, 1542, 10.1126/science.1083430 Uziel, 2003, Requirement of the MRN complex for ATM activation by DNA damage, EMBO J., 22, 5612, 10.1093/emboj/cdg541 Yang, 2004, ATM and ATR: Sensing DNA damage, World J. Gastroenterol, 10, 155, 10.3748/wjg.v10.i2.155 Cimprich, 2008, ATR: an essential regulator of genome integrity, Nat. Rev. Mol. Cell Biol., 9, 616, 10.1038/nrm2450 Eich, 2013, Contribution of ATM and ATR to the resistance of glioblastoma and malignant melanoma cells to the methylating anticancer drug temozolomide, Mol. Cancer Ther., 12, 2529, 10.1158/1535-7163.MCT-13-0136 Marechal, 2013, DNA Damage Sensing by the ATM and ATR Kinases, Cold Spring Harb. Perspect. Biol., 5, 10.1101/cshperspect.a012716 Zeman, 2014, Causes and consequences of replication stress, Nat. Cell Biol., 16, 2, 10.1038/ncb2897 Espinosa-Diez, 2018, MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling, Cell Death Dis, 9, 632, 10.1038/s41419-018-0690-y Rombouts, 2013, Differential response to acute low dose radiation in primary and immortalized endothelial cells, Int. J. Radiat. Biol., 89, 841, 10.3109/09553002.2013.806831 Petroni, 2016, The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress, Cell Death Differ, 23, 197, 10.1038/cdd.2015.81 Hu, 2010, ATM is down-regulated by N-Myc-regulated microRNA-421, Proc. Natl. Acad. Sci., 107, 1506, 10.1073/pnas.0907763107 Chen, 2018, Radiosensitizing effects of miR-18a-5p on lung cancer stem-like cells via downregulating both ATM and HIF-1α, Cancer Med., 7, 3834, 10.1002/cam4.1527 Wu, 2020, Radiosensitization of hepatocellular carcinoma through targeting radio-associated MicroRNA, Int. J. Mol. Sci., 21, 1859, 10.3390/ijms21051859 Rahman, 2014, miR-15b/16-2 Regulates Factors That Promote p53 Phosphorylation and Augments the DNA Damage Response following Radiation in the Lung, J. Biol. Chem., 289, 26406, 10.1074/jbc.M114.573592 Zhan, 2017, MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1-ATM-p53 feedback loop, Oncotarget, 8, 54788, 10.18632/oncotarget.18510 Kaufmann, S.H., Desnoyers, S., Ottaviano, Y., Davidson, N.E. & Poirier, G.G. Specific Proteolytic Cleavage of Poly(ADP-ribose) Polymerase: An Early Marker of Chemotherapy-induced Apoptosis. 11. Ofir, 2011, miR-15 and miR-16 Are Direct Transcriptional Targets of E2F1 that Limit E2F-Induced Proliferation by Targeting Cyclin E, Mol. Cancer Res., 9, 440, 10.1158/1541-7786.MCR-10-0344 Cimmino, 2005, miR-15 and miR-16 induce apoptosis by targeting BCL2, Proc. Natl. Acad. Sci., 102, 13944, 10.1073/pnas.0506654102 Simone, 2009, Ionizing radiation-induced oxidative stress alters miRNA expression, PLoS One, 4, 10.1371/journal.pone.0006377 Liao, 2015, STAT3 regulated ATR via microRNA-383 to control DNA damage to affect apoptosis in A431 cells, Cell. Signal., 27, 2285, 10.1016/j.cellsig.2015.08.005 Xie, 2014, Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma, Med. Oncol., 31, 844, 10.1007/s12032-014-0844-4 Liu, 2015, MiR-195 suppresses non-small cell lung cancer by targeting CHEK1, Oncotarget, 6, 9445, 10.18632/oncotarget.3255 Lezina, 2013, miR-16 and miR-26a target checkpoint kinases Wee1 and Chk1 in response to p53 activation by genotoxic stress, Cell Death Dis, 4, 953, 10.1038/cddis.2013.483 Duan, 2018, Wee1 kinase inhibitor MK‑1775 induces apoptosis of acute lymphoblastic leukemia cells and enhances the efficacy of doxorubicin involving downregulation of Notch pathway, Oncol. Lett., 10.3892/ol.2018.9291 Kitadate, 2016, MicroRNA-16 mediates the regulation of a senescence–apoptosis switch in cutaneous T-cell and other non-Hodgkin lymphomas, Oncogene, 35, 3692, 10.1038/onc.2015.435 Gupta, 2020, Integrative data modeling from lung and lymphatic cancer predicts functional roles for miR-34a and miR-16 in cell fate regulation, Sci. Rep., 10, 2511, 10.1038/s41598-020-59339-y Bao, 2018, MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway, Cell Death Dis, 9, 1045, 10.1038/s41419-018-1020-0 Krishnan, 2013, MicroRNA-182-5p targets a network of genes involved in DNA repair, RNA, 19, 230, 10.1261/rna.034926.112 Zhang, 2004, Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair, Mol. Cell. Biol., 24, 708, 10.1128/MCB.24.2.708-718.2004 Stolz, 2011, Tumor Suppressor CHK2: Regulator of DNA Damage Response and Mediator of Chromosomal Stability: Fig. 1, Clin. Cancer Res., 17, 401, 10.1158/1078-0432.CCR-10-1215 Zou, 2002, Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin, Genes Dev., 16, 198, 10.1101/gad.950302 Ward, 2003, p53 Binding Protein 53BP1 Is Required for DNA Damage Responses and Tumor Suppression in Mice, Mol. Cell. Biol., 23, 2556, 10.1128/MCB.23.7.2556-2563.2003 Harding, 2011, ATM-dependent phosphorylation of 53BP1 in response to genomic stress in oxic and hypoxic cells, Radiother. Oncol., 99, 307, 10.1016/j.radonc.2011.05.039 Shiotani, 2013, Two Distinct Modes of ATR Activation Orchestrated by Rad17 and Nbs1, Cell Rep., 3, 1651, 10.1016/j.celrep.2013.04.018 Huang, 2015, MicroRNA-191 promotes osteosarcoma cells proliferation by targeting checkpoint kinase 2, Tumor Biol., 36, 6095, 10.1007/s13277-015-3290-9 Yang, L., Zhao, W., Wei, P., Zuo, W. & Zhu, S. Tumor suppressor p53 induces miR-15a processing to inhibit neuronal apoptosis inhibitory protein (NAIP) in the apoptotic response DNA damage in breast cancer cell. 9. Sachdeva, 2009, p53 represses c-Myc through induction of the tumor suppressor miR-145, Proc. Natl. Acad. Sci., 106, 3207, 10.1073/pnas.0808042106 Xiao, 2011, miR-605 joins p53 network to form a p53: miR-605:Mdm2 positive feedback loop in response to stress: miR-605 in the p53 gene network, EMBO J., 30, 524, 10.1038/emboj.2010.347 Barsotti, 2012, p53-dependent Induction of PVT1 and miR-1204, J. Biol. Chem., 287, 2509, 10.1074/jbc.M111.322875 Suzuki, 2009, Modulation of microRNA processing by p53, Nature, 460, 529, 10.1038/nature08199 Moll, 2003, The MDM2-p53 interaction, Mol. Cancer Res. MCR, 1, 1001 Zhang, 2015, The regulation of the p53/MDM2 feedback loop by microRNAs, RNA Dis., 2, 502 Lev Bar-Or, 2000, Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study, Proc. Natl. Acad. Sci., 97, 11250, 10.1073/pnas.210171597 Moore, 2015, MiR-192-mediated positive feedback loop controls the robustness of stress-induced p53 oscillations in breast cancer cells, PLOS Comput. Biol., 11, 10.1371/journal.pcbi.1004653 Zhang, 2009, Cell fate decision mediated by p53 pulses, Proc. Natl. Acad. Sci., 106, 12245, 10.1073/pnas.0813088106 Batchelor, 2011, Stimulus‐dependent dynamics of p53 in single cells, Mol. Syst. Biol., 7, 488, 10.1038/msb.2011.20 Zhang, 2011, Two-phase dynamics of p53 in the DNA damage response, Proc. Natl. Acad. Sci., 108, 8990, 10.1073/pnas.1100600108 Chen, 2013, DNA damage strength modulates a bimodal switch of p53 dynamics for cell-fate control, BMC Biol., 11, 73, 10.1186/1741-7007-11-73 Luo, 2017, Dynamics of p53: a master decider of cell fate, Genes, 8, 66, 10.3390/genes8020066 Gupta, 2020, Towards DNA-damage induced autophagy: A Boolean model of p53-induced cell fate mechanisms, DNA Repair., 96, 10.1016/j.dnarep.2020.102971 Porter, 2016, p53 pulses diversify target gene expression dynamics in an mRNA half-life-dependent manner and delineate co-regulated target gene subnetworks, Cell Syst., 2, 272, 10.1016/j.cels.2016.03.006 Bommer, 2007, p53-mediated activation of miRNA34 candidate tumor-suppressor genes, Curr. Biol., 17, 1298, 10.1016/j.cub.2007.06.068 Chang, 2007, Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis, Mol. Cell, 26, 745, 10.1016/j.molcel.2007.05.010 Braun, 2008, p53-Responsive MicroRNAs 192 and 215 Are Capable of Inducing Cell Cycle Arrest, Cancer Res., 68, 10094, 10.1158/0008-5472.CAN-08-1569 Pichiorri, 2010, Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development, Cancer Cell, 18, 367, 10.1016/j.ccr.2010.09.005 Ugalde, 2011, Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53: Regulatory circuitry involving miR-29 and p53, EMBO J., 30, 2219, 10.1038/emboj.2011.124 Zhang, 2013, Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop, Oncogene, 9 Zhou, 2014, Involvement of miR-605 and miR-34a in the DNA damage response promotes apoptosis induction, Biophys. J., 106, 1792, 10.1016/j.bpj.2014.02.032 Jia, 2019, MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1, Exp. Cell Res., 375, 73, 10.1016/j.yexcr.2018.12.016 Lu, 2005, Reversal of the ATM/ATR-mediated DNA damage response by the oncogenic phosphatase PPM1D, Cell Cycle, 4, 4060, 10.4161/cc.4.8.1876 D'orazi, 2002, Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis, Nat. Cell Biol., 4, 11, 10.1038/ncb714 Huang, 2015, miR-141 regulates TGF-β1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells, Int. J. Mol. Med., 35, 311, 10.3892/ijmm.2014.2008 Lizé, 2010, E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis, Cell Death Differ, 17, 452, 10.1038/cdd.2009.188 Hu, 2014, miR-449a regulates proliferation and chemosensitivity to cisplatin by targeting cyclin D1 and BCL2 in SGC7901 cells, Dig. Dis. Sci., 59, 336, 10.1007/s10620-013-2923-3 Dubrez, 2017, Regulation of E2F1 transcription factor by ubiquitin conjugation, Int. J. Mol. Sci., 18, 2188, 10.3390/ijms18102188 Biswas, 2012, Transcriptional and Nontranscriptional Functions of E2F1 in Response to DNA Damage: Fig. 1, Cancer Res., 72, 13, 10.1158/0008-5472.CAN-11-2196 Stiewe, 2000, Role of the p53-homologue p73 in E2F1-induced apoptosis, Nat. Genet., 26, 464, 10.1038/82617 Xia, 2020, MicroRNA-506-3p inhibits proliferation and promotes apoptosis in ovarian cancer cell via targeting SIRT1/AKT/FOXO3a signaling pathway, Neoplasma, 67, 344, 10.4149/neo_2020_190517N441 Santo, 2013, FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma, Cancer Res., 73, 2189, 10.1158/0008-5472.CAN-12-3767 Burgering, 2003, Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty, J. Leukoc. Biol., 73, 689, 10.1189/jlb.1202629 Sanphui, 2013, FoxO3a is activated and executes neuron death via Bim in response to β-amyloid, Cell Death Dis, 4, 625, 10.1038/cddis.2013.148 Haque, 2020, Downregulation of miR-506-3p facilitates EGFR-TKI resistance through induction of sonic hedgehog signaling in non-small-cell lung cancer cell lines, Int. J. Mol. Sci., 21, 9307, 10.3390/ijms21239307 Bartek, 2001, Mammalian G1- and S-phase checkpoints in response to DNA damage, Curr. Opin. Cell Biol., 13, 738, 10.1016/S0955-0674(00)00280-5 Löbrich, 2007, The impact of a negligent G2/M checkpoint on genomic instability and cancer induction, Nat. Rev. Cancer, 7, 861, 10.1038/nrc2248 Hermeking, 1997, 14-3-3σ Is a p53-Regulated Inhibitor of G2/M Progression, Mol. Cell, 1, 3, 10.1016/S1097-2765(00)80002-7 Liu, 2020, The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review, Cancer Cell Int., 20, 213, 10.1186/s12935-020-01304-w Mobarra, 2015, Overexpression of microRNA-16 declines cellular growth, proliferation and induces apoptosis in human breast cancer cells, Vitro Cell. Dev. Biol. - Anim, 51, 604, 10.1007/s11626-015-9872-4 Liu, 2008, miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes, Nucleic Acids Res., 36, 5391, 10.1093/nar/gkn522 Yan, 2012, Dynamical Behaviors of Rb-E2F Pathway Including Negative Feedback Loops Involving miR449, PLoS One, 7, 10.1371/journal.pone.0043908 Gillies, 2007, Regulation of p27 Kip1 by miRNA 221/222 in Glioblastoma, Cell Cycle, 6, 2005, 10.4161/cc.6.16.4526 Dolezalova, 2012, MicroRNAs Regulate p21Waf1/Cip1 Protein Expression and the DNA Damage Response in Human Embryonic Stem Cells, Stem Cells, 30, 1362, 10.1002/stem.1108 Abbas, 2009, p21 in cancer: intricate networks and multiple activities, Nat. Rev. Cancer, 9, 400, 10.1038/nrc2657 Liu, 2014, Stem cells: balancing resistance and sensitivity to DNA damage, Trends Cell Biol., 24, 268, 10.1016/j.tcb.2014.03.002 Ivanovska, 2008, MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression, Mol. Cell. Biol., 28, 2167, 10.1128/MCB.01977-07 Xu, 2016, DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21 WAF1/CIP1, Cell Cycle, 15, 2920, 10.1080/15384101.2016.1224043 Scharer, 2013, Nucleotide excision repair in eukaryotes, Cold Spring Harb. Perspect. Biol., 5, 10.1101/cshperspect.a012609 Rocha, 2018, DNA repair pathways and cisplatin resistance: an intimate relationship, Clinics, 73, 478, 10.6061/clinics/2018/e478s Robu, 2013, Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair, Proc. Natl. Acad. Sci., 110, 1658, 10.1073/pnas.1209507110 Reynolds, 2015, Disruption of PARP1 function inhibits base excision repair of a sub-set of DNA lesions, Nucleic Acids Res., 43, 4028, 10.1093/nar/gkv250 Hu, 2014, PARP1-Driven Poly-ADP-Ribosylation Regulates BRCA1 Function in Homologous Recombination–Mediated DNA Repair, Cancer Discov., 4, 1430, 10.1158/2159-8290.CD-13-0891 Lai, 2019, MiR-7-5p-mediated downregulation of PARP1 impacts DNA homologous recombination repair and resistance to doxorubicin in small cell lung cancer, BMC Cancer, 19, 602, 10.1186/s12885-019-5798-7 Luo, 2018, miR-7-5p overexpression suppresses cell proliferation and promotes apoptosis through inhibiting the ability of DNA damage repair of PARP-1 and BRCA1 in TK6 cells exposed to hydroquinone, Chem. Biol. Interact., 283, 84, 10.1016/j.cbi.2018.01.019 Huang, 2013, Systematic Screen Identifies miRNAs That Target RAD51 and RAD51D to Enhance Chemosensitivity, Mol. Cancer Res., 11, 1564, 10.1158/1541-7786.MCR-13-0292 Wilson, 2016, MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment, Nat. Commun., 7, 13597, 10.1038/ncomms13597 Miyazaki, 2014, The 3′–5′ DNA Exonuclease TREX1 Directly Interacts with Poly(ADP-ribose) Polymerase-1 (PARP1) during the DNA Damage Response, J. Biol. Chem., 289, 32548, 10.1074/jbc.M114.547331 Chen, 2019, MiR-34s negatively regulate homologous recombination through targeting RAD51, Arch. Biochem. Biophys., 666, 73, 10.1016/j.abb.2019.03.017 Piotto, 2018, Functional validation of miRNAs targeting genes of DNA double-strand break repair to radiosensitize non-small lung cancer cells, Biochim. Biophys. Acta BBA - Gene Regul. Mech, 1861, 1102, 10.1016/j.bbagrm.2018.10.010 Li, 2020, miR-623 suppresses cell proliferation, migration and invasion through direct inhibition of XRCC5 in breast cancer, Aging, 12, 10246, 10.18632/aging.103182 Zhang, 2015, By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer, Oncotarget, 6, 1462, 10.18632/oncotarget.2808 Bukeirat, 2016, MiR-34a regulates blood–brain barrier permeability and mitochondrial function by targeting cytochrome c, J. Cereb. Blood Flow Metab., 36, 387, 10.1177/0271678X15606147 Edlich, 2018, BCL-2 proteins and apoptosis: Recent insights and unknowns, Biochem. Biophys. Res. Commun., 500, 26, 10.1016/j.bbrc.2017.06.190 Cheng, 2018, Downregulation of microRNA‑1 attenuates glucose‑induced apoptosis by regulating the liver X receptor α in cardiomyocytes, Exp. Ther. Med., 16, 1814 Zaman, 2010, The functional significance of microRNA-145 in prostate cancer, Br. J. Cancer, 103, 256, 10.1038/sj.bjc.6605742 Wu, 2002, Killer/DR5, a novel DNA-damage inducible death receptor gene, links the p53-tumor suppressor to caspase activation and apoptotic death, vol. 465, 143 Wang, 2003, TRAIL and apoptosis induction by TNF-family death receptors, Oncogene, 22, 8628, 10.1038/sj.onc.1207232 Spizzo, 2010, miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells, Cell Death Differ., 17, 246, 10.1038/cdd.2009.117 Li, 2016, MicroRNA-143 promotes apoptosis of osteosarcoma cells by caspase-3 activation via targeting Bcl-2, Biomed. Pharmacother., 80, 8, 10.1016/j.biopha.2016.03.001 Shanesazzade, 2018, & Nasr Esfahani, M. H. miR-34a/BCL-2 signaling axis contributes to apoptosis in MPP + -induced SH-SY5Y cells, Mol. Genet. Genomic Med., 6, 975, 10.1002/mgg3.469 Tsuchiya, 2011, Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21, Cancer Res., 71, 4628, 10.1158/0008-5472.CAN-10-2475 Yu, 2018, Neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage, Int. J. Mol. Med., 41, 2406 Zhang, 2018, Insulin‑like growth factor 1/insulin‑like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells, Exp. Ther. Med., 16, 1477 Zhang, 2017, Tumor suppressive role of miR-194-5p in glioblastoma multiforme, Mol. Med. Rep., 16, 9317, 10.3892/mmr.2017.7826 Cao, 2017, miRNA-504 inhibits p53-dependent vascular smooth muscle cell apoptosis and may prevent aneurysm formation, Mol. Med. Rep., 16, 2570, 10.3892/mmr.2017.6873 Li, 2011, MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells, Gynecol. Oncol., 120, 145, 10.1016/j.ygyno.2010.09.009 Cheng, 2016, MiRNA-183-5p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting the PDCD4, Reprod. Biol., 16, 225, 10.1016/j.repbio.2016.07.002 Wang, 2019, Programmed cell death factor 4 enhances the chemosensitivity of colorectal cancer cells to Taxol, Oncol. Lett., 18, 1402 Eto, 2012, Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA, Cell Death Differ., 19, 573, 10.1038/cdd.2011.126 Lu, 2015, miRNA-24-3p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting p27Kip1, Oncol. Rep., 34, 995, 10.3892/or.2015.4025 Li, 2018, microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle, Proc. Natl. Acad. Sci., 115, E10849, 10.1073/pnas.1803377115 Zang, 2012, MiR-155 inhibits the sensitivity of lung cancer cells to cisplatin via negative regulation of Apaf-1 expression, Cancer Gene Ther., 19, 773, 10.1038/cgt.2012.60 Mai, 2019, The combination therapy of HIF1α inhibitor LW6 and cisplatin plays an effective role on anti-tumor function in A549 cells, Neoplasma, 66, 776, 10.4149/neo_2018_180921N708 Grieco, 2017, MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells, Diabetes, 66, 100, 10.2337/db16-0592 Jaiswal, 2000, Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism, Cancer Res., 60, 184 Pernaute, 2014, MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM, Genes Dev., 28, 1873, 10.1101/gad.245621.114 Zhang, 2014, Knockdown of miR-214 promotes apoptosis and inhibits cell proliferation in nasopharyngeal carcinoma, PLoS One, 9 Floyd, 2014, Novel anti-apoptotic MicroRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and bim, PLoS One, 9, 10.1371/journal.pone.0096239 Jin, 2018, CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3, Cell Death Dis., 9, 318, 10.1038/s41419-018-0350-2 Razumilava, 2012, miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma, Hepatology, 55, 465, 10.1002/hep.24698 Peng, 2015, miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL, Mol. Cell. Biochem., 409, 103, 10.1007/s11010-015-2516-x Schulze-Osthoff, 1998, Apoptosis signaling by death receptors, Eur. J. Biochem., 254, 439, 10.1046/j.1432-1327.1998.2540439.x Wang, 2011, Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3, J. Pathol., 225, 232, 10.1002/path.2931 Jayarama, 2014, MADD Is a Downstream Target of PTEN in Triggering Apoptosis: MADD Is a Downstream Target of PTEN, J. Cell. Biochem., 115, 261, 10.1002/jcb.24657 Chai, 2018, MicroRNA-498 promotes proliferation and migration by targeting the tumor suppressor PTEN in breast cancer cells, Carcinogenesis, 39, 1185, 10.1093/carcin/bgy092 Chen, 2017, MicroRNAs tend to synergistically control expression of genes encoding extensively-expressed proteins in humans, PeerJ, 5, 10.7717/peerj.3682 Zamaraeva, 2005, Cells die with increased cytosolic ATP during apoptosis: a bioluminescence study with intracellular luciferase, Cell Death Differ., 12, 1390, 10.1038/sj.cdd.4401661 Elmore, 2007, Apoptosis: a review of programmed cell death, Toxicol. Pathol., 35, 495, 10.1080/01926230701320337 Raut, 2016, miR-30c and miR-181a synergistically modulate p53–p21 pathway in diabetes induced cardiac hypertrophy, Mol. Cell. Biochem., 417, 191, 10.1007/s11010-016-2729-7 Yoda, 2010, ATP-dependent human RISC assembly pathways, Nat. Struct. Mol. Biol., 17, 17, 10.1038/nsmb.1733 Niu, 2016, MiR-29c regulates the expression of miR-34c and miR-449a by targeting DNA methyltransferase 3a and 3b in nasopharyngeal carcinoma, BMC Cancer, 16, 218, 10.1186/s12885-016-2253-x Zeng, 2014, MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells, FEBS Lett., 588, 4677, 10.1016/j.febslet.2014.10.040 Krek, 2005, Combinatorial microRNA target predictions, Nat. Genet., 37, 495, 10.1038/ng1536 Lewis, 2005, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are MicroRNA targets, Cell, 120, 15, 10.1016/j.cell.2004.12.035 Yang, 2011, starBase: a database for exploring microRNA–mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data, Nucleic Acids Res., 39, D202, 10.1093/nar/gkq1056 Kern, 2021, miRTargetLink 2.0—interactive miRNA target gene and target pathway networks, Nucleic Acids Res., 49, W409, 10.1093/nar/gkab297 Acharya, 2015, Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury, Sci. Transl. Med., 7, 287, 10.1126/scitranslmed.aaa6593 Ren, 2017, MicroRNA-187 regulates gastric cancer progression by targeting the tumor suppressor CRMP1, Biochem. Biophys. Res. Commun., 482, 597, 10.1016/j.bbrc.2016.11.079 Lang, 2018, MicroRNA‑96 expression induced by low‑dose cisplatin or doxorubicin regulates chemosensitivity, cell death and proliferation in gastric cancer SGC7901 cells by targeting FOXO1, Oncol. Lett., 16, 4020 Leslie, 2018, p53 regulates the expression of LRP1 and apoptosis through a stress intensity-dependent MicroRNA feedback loop, Cell Rep., 24, 1484, 10.1016/j.celrep.2018.07.010 Visser, 2021, MicroRNAs, damage levels, and DNA damage response control, Trends Genet., 37, 963, 10.1016/j.tig.2021.06.018 Lu, 2020, Circular RNA HIPK3 induces cell proliferation and inhibits apoptosis in non-small cell lung cancer through sponging miR-149, Cancer Biol. Ther., 21, 113, 10.1080/15384047.2019.1669995 Lai, 2020, CircHIPK3 promotes proliferation and metastasis and inhibits apoptosis of renal cancer cells by inhibiting MiR-485-3p, Cancer Cell Int., 20, 248, 10.1186/s12935-020-01319-3 Song, 2017, Long non-coding RNA XIST functions as an oncogene in human colorectal cancer by targeting miR-132-3p, J. BUON Off. J. Balk. Union Oncol., 22, 696 Sun, 2018, Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway, Gene, 665, 141, 10.1016/j.gene.2018.04.014 Zhang, 2017, The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer: This article has been corrected since Advanced Online Publication, and an erratum is also printed in this issue, Acta Pharmacol. Sin., 38, 371, 10.1038/aps.2016.133 Laurent, 2015, Differential DNA damage signalling and apoptotic threshold correlate with mouse epiblast-specific hypersensitivity to radiation, Development, 142, 3675 Ludwig, 2016, Distribution of miRNA expression across human tissues, Nucleic Acids Res., 44, 3865, 10.1093/nar/gkw116 Bonneau, 2019, How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market, EJIFCC, 30, 114 Mao, 2012, Modulation of microRNA processing by mismatch repair protein MutLα, Cell Res., 22, 973, 10.1038/cr.2012.18 Stojic, 2004, Mismatch repair and DNA damage signalling, DNA Repair, 3, 1091, 10.1016/j.dnarep.2004.06.006 Li, 1999, The role of mismatch repair in DNA damage-induced apoptosis, Oncol. Res., 11, 393 Karran, 1994, DNA damage tolerance, mismatch repair and genome instability, BioEssays, 16, 833, 10.1002/bies.950161110 Hsieh, 2008, DNA mismatch repair: Molecular mechanism, cancer, and ageing, Mech. Ageing Dev., 129, 391, 10.1016/j.mad.2008.02.012 Guan, 2021, MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway, Cancer Cell, 39, 109, 10.1016/j.ccell.2020.11.004 Le, 2015, PD-1 blockade in tumors with mismatch-repair deficiency, N. Engl. J. Med., 372, 2509, 10.1056/NEJMoa1500596 Le, 2017, Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade, Science, 357, 409, 10.1126/science.aan6733 Lu, 2021, DNA sensing in mismatch repair-deficient tumor cells is essential for anti-tumor immunity, Cancer Cell, 39, 96, 10.1016/j.ccell.2020.11.006 Fink, 1998, The role of DNA mismatch repair in drug resistance, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, 4, 1 Valeri, 2010, Modulation of mismatch repair and genomic stability by miR-155, Proc. Natl. Acad. Sci., 107, 6982, 10.1073/pnas.1002472107 Mattiske, 2012, The oncogenic role of miR-155 in breast cancer, Cancer Epidemiol. Biomarkers Prev., 21, 1236, 10.1158/1055-9965.EPI-12-0173 Valeri, 2010, MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2), Proc. Natl. Acad. Sci., 107, 21098, 10.1073/pnas.1015541107 Zhao, 2019, Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy, J. Hematol. Oncol., 12, 54, 10.1186/s13045-019-0738-1 Ashizawa, 2019, microRNA-148a-3p regulates immunosuppression in DNA mismatch repair-deficient colorectal cancer by targeting PD-L1, Mol. Cancer Res. Mol., 17, 1403, 10.1158/1541-7786.MCR-18-0831 Zhang, 2021, The growth of siRNA-based therapeutics: Updated clinical studies, Biochem. Pharmacol., 189, 10.1016/j.bcp.2021.114432 Saini, 2021, Can microRNA become next-generation tools in molecular diagnostics and therapeutics? A systematic review. Egypt, J. Med. Hum. Genet., 22, 4, 10.1186/s43042-020-00125-w Hanna, 2019, The potential for microRNA therapeutics and clinical research, Front. Genet., 10, 478, 10.3389/fgene.2019.00478 Chakraborty, 2021, Therapeutic advances of miRNAs: a preclinical and clinical update, J. Adv. Res., 28, 127, 10.1016/j.jare.2020.08.012 Zhang, 2021, The risks of miRNA therapeutics: in a drug target perspective, Drug Des. Devel. Ther., Volume 15, 721, 10.2147/DDDT.S288859 Hong, 2020, Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours, Br. J. Cancer, 122, 1630, 10.1038/s41416-020-0802-1