CoChat
Sign Up
Cited by 59MicroRNA in disease regulationCancer-related molecular mechanisms researchCancer-related Molecular Pathways

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

Open access
Xu, Shun, Huang, Haijiao, Chen, Yu-ning, Deng, Yun-ting, Zhang, Bing, Xiong, Xing-dong, Yuan, Yuan, Zhu, Yanmei +3 more·2016·Cell Cycle
DOI 10.1080/15384101.2016.1224043PMC PMC5105918
Open this paper in CoChat — free accountOpen PDF

Abstract

Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down-regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR-33b-3p endowed the lung cancer cells with enhanced survival and decreased γH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1080/15384101.2016.1224043

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. Cline SD, Hanawalt PC. Who's on first in the cellular response to DNA damage? Nat Rev Mol Cell Biol 2003; 4:361-72; PMID:12728270; http://dx.doi.org/10.1038/nrm1101 · DOI · Paper page
  2. Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 2009; 461:1071-8; PMID:19847258; http://dx. doi.org/10.1038/nature08467 · DOI · Paper page
  3. Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med 2009; 361:1475-85; PMID:19812404; http://dx.doi.org/10.1056/ NEJMra0804615 · DOI · Paper page
  4. Lord CJ, Ashworth A. The DNA damage response and cancer ther- apy. Nature 2012; 481:287-94; PMID:22258607; http://dx.doi.org/ 10.1038/nature10760 · DOI
  5. Reed E. Platinum-DNA adduct, nucleotide excision repair and plati- num based anti-cancer chemotherapy. Cancer Treat Rev 1998; 24:331-44; PMID:9861196; http://dx.doi.org/10.1016/S0305-7372 (98)90056-1 · DOI
  6. Sears CR, Cooney SA, Chin-Sinex H, Mendonca MS, Turchi JJ. DNA damage response (DDR) pathway engagement in cisplatin radiosensitization of non-small cell lung cancer. DNA Repair (Amst) 2016; 40:35-46; PMID:26991853; http://dx.doi.org/10.1016/j. dnarep.2016.02.004 · DOI
  7. van Jaarsveld MT, Wouters MD, Boersma AW, Smid M, van Ijcken WF, Mathijssen RH, Hoeijmakers JH, Martens JW, van Laere S, Wiemer EA, et al. DNA damage responsive microRNAs misex- pressed in human cancer modulate therapy sensitivity. Mol Oncol 2014; 8:458-68; PMID:24462518; http://dx.doi.org/10.1016/j. molonc.2013.12.011 · DOI
  8. Qian W, Wang J, Roginskaya V, McDermott LA, Edwards RP, Stolz DB, Llambi F, Green DR, Van Houten B. Novel combination of mitochondrial division inhibitor 1 (mdivi-1) and platinum agents produces synergistic pro-apoptotic effect in drug resistant tumor cells. Oncotarget 2014; 5:4180-94; PMID:24952704; http://dx.doi. org/10.18632/oncotarget.1944 · DOI
  9. Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 2005; 4:307-20; PMID:15789122; http:// dx.doi.org/10.1038/nrd1691 · DOI · Paper page
  10. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and func- tion. Cell 2004; 116:281-97; PMID:14744438; http://dx.doi.org/ 10.1016/S0092-8674(04)00045-5 · DOI
  11. Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 2005; 6:376-85; PMID:15852042; http://dx. doi.org/10.1038/nrm1644 · DOI · Paper page
  12. Shenoy A, Blelloch RH. Regulation of microRNA function in somatic stem cell proliferation and differentiation. Nat Rev Mol Cell Biol 2014; 15:565-76; PMID:25118717; http://dx.doi.org/ 10.1038/nrm3854 · DOI
  13. Goedeke L, Aranda JF, Fernandez-Hernando C. microRNA regula- tion of lipoprotein metabolism. Curr Opin Lipidol 2014; 25:282-8; PMID:24978143; http://dx.doi.org/10.1097/MOL.0000000000000094 · DOI
  14. Wan G, Mathur R, Hu X, Zhang X, Lu X. miRNA response to DNA damage. Trends Biochem Sci 2011; 36:478-84; PMID:21741842; http://dx.doi.org/10.1016/j.tibs.2011.06.002 · DOI
  15. Mueller AC, Sun D, Dutta A. The miR-99 family regulates the DNA damage response through its target SNF2H. Oncogene 2013; 32:1164-72; PMID:22525276; http://dx.doi.org/10.1038/onc.2012.131 · DOI
  16. Pothof J, Verkaik NS, van IW, Wiemer EA, Ta VT, van der Horst GT, Jaspers NG, van Gent DC, Hoeijmakers JH, Persengiev SP. MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response. EMBO J 2009; 28:2090-9; PMID:19536137; http://dx.doi.org/10.1038/emboj.2009.156 · DOI
  17. Liu Y, Li Y, Lu X. Regulators in the DNA damage response. Arch Biochem Biophys 2016; 594:18-25; PMID:26882840; http://dx.doi. org/10.1016/j.abb.2016.02.018 · DOI
  18. Heacock ML, Stefanick DF, Horton JK, Wilson SH. Alkylation DNA damage in combination with PARP inhibition results in for- mation of S-phase-dependent double-strand breaks. DNA Repair (Amst) 2010; 9:929-36; PMID:20573551; http://dx.doi.org/10.1016/j. dnarep.2010.05.007 · DOI
  19. Li S. Implication of posttranslational histone modifications in nucle- otide excision repair. Int J Mol Sci 2012; 13:12461-86; PMID:23202908; http://dx.doi.org/10.3390/ijms131012461 · DOI
  20. Li A, Yu Y, Lee SC, Ishibashi T, Lees-Miller SP, Ausio J. Phosphory- lation of histone H2A.X by DNA-dependent protein kinase is not affected by core histone acetylation, but it alters nucleosome stability and histone H1 binding. J Biol Chem 2010; 285:17778-88; PMID:20356835; http://dx.doi.org/10.1074/jbc.M110.116426 · DOI
  21. Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH, Pommier Y. Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res 2002; 62:4899-902; PMID:12208738
  22. Martin NT, Nakamura K, Davies R, Nahas SA, Brown C, Tunuguntla R, Gatti RA, Hu H. ATM-dependent MiR-335 targets CtIP and mod- ulates the DNA damage response. PLoS Genet 2013; 9:e1003505; PMID:23696749; http://dx.doi.org/10.1371/journal.pgen.1003505 · DOI
  23. Rahman M, Lovat F, Romano G, Calore F, Acunzo M, Bell EH, Nana-Sinkam P. miR-15b/16-2 regulates factors that promote p53 phosphorylation and augments the DNA damage response following radiation in the lung. J Biol Chem 2014; 289:26406-16; PMID:25092292; http://dx.doi.org/10.1074/jbc.M114.573592 · DOI
  24. Xie QH, He XX, Chang Y, Sun SZ, Jiang X, Li PY, Lin JS. MiR-192 inhibits nucleotide excision repair by targeting ERCC3 and ERCC4 in HepG2.2.15 cells. Biochem Biophys Res Commun 2011; 410:440- 5; PMID:21672525; http://dx.doi.org/10.1016/j.bbrc.2011.05.153 · DOI
  25. Huang JW, Wang Y, Dhillon KK, Calses P, Villegas E, Mitchell PS, Tewari M, Kemp CJ, Taniguchi T. Systematic screen identifies miR- NAs that target RAD51 and RAD51D to enhance chemosensitivity. Mol Cancer Res 2013; 11:1564-73; PMID:24088786; http://dx.doi. org/10.1158/1541-7786.MCR-13-0292 · DOI
  26. Rolfo C, Fanale D, Hong DS, Tsimberidou AM, Piha-Paul SA, Pau- wels P, Van Meerbeeck JP, Caruso S, Bazan V, Cicero G, et al. Impact of microRNAs in resistance to chemotherapy and novel tar- geted agents in non-small cell lung cancer. Curr Pharm Biotechnol 2014; 15:475-85; PMID:24846062; http://dx.doi.org/10.2174/ 1389201015666140519123219 · DOI
  27. Dong Z, Zhong Z, Yang L, Wang S, Gong Z. MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9. Cancer Lett 2014; 343:249- 57; PMID:24099915; http://dx.doi.org/10.1016/j.canlet.2013.09.034 · DOI
  28. Zang YS, Zhong YF, Fang Z, Li B, An J. MiR-155 inhibits the sensi- tivity of lung cancer cells to cisplatin via negative regulation of Apaf- 1 expression. Cancer Gene Ther 2012; 19:773-8; PMID:22996741; http://dx.doi.org/10.1038/cgt.2012.60 · DOI
  29. Bian HB, Pan X, Yang JS, Wang ZX, De W. Upregulation of micro- RNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549). J Exp Clin Cancer Res 2011; 30:20; PMID:21329503; http://dx.doi.org/10.1186/1756-9966-30-20 · DOI
  30. Xiang Q, Tang H, Yu J, Yin J, Yang X, Lei X. MicroRNA-98 sensitizes cisplatin-resistant human lung adenocarcinoma cells by up-regula- tion of HMGA2. Pharmazie 2013; 68:274-81; PMID:23700794
  31. Pines J. Cell cycle. p21 inhibits cyclin shock. Nature 1994; 369:520-1; PMID:7911227; http://dx.doi.org/10.1038/369520a0 · DOI
  32. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998; 282:1497-501; PMID:9822382; http://dx.doi.org/10.1126/science.282.5393.1497 · DOI · Paper page
  33. Gorospe M, Wang X, Guyton KZ, Holbrook NJ. Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells. Mol Cell Biol 1996; 16:6654-60; PMID:8943319; http://dx.doi.org/10.1128/MCB.16.12.6654 · DOI
  34. Wei J, Zhao J, Long M, Han Y, Wang X, Lin F, Ren J, He T, Zhang H. p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carci- noma cell. BMC Cancer 2010; 10:632; PMID:21087528; http://dx.doi. org/10.1186/1471-2407-10-632 · DOI
  35. Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM. Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc Natl Acad Sci U S A 2000; 97:9042-6; PMID:10908655; http://dx.doi.org/10.1073/pnas.160016897 · DOI
  36. Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, De W, Wang Z, Wang R. The long noncoding RNA HOTAIR contributes to cisplatin resis- tance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One 2013; 8:e77293; PMID:24155936; http://dx.doi.org/10.1371/journal.pone.0077293 · DOI
  37. Zheng L, Zhang Y, Liu Y, Zhou M, Lu Y, Yuan L, Zhang C, Hong M, Wang S, Li X. MiR-106b induces cell radioresistance via the PTEN/ PI3K/AKT pathways and p21 in colorectal cancer. J Transl Med 2015; 13:252; PMID:26238857; http://dx.doi.org/10.1186/s12967- 015-0592-z · DOI
  38. Zhang Y, Geng L, Talmon G, Wang J. MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer. J Biol Chem 2015; 290:6215-25; PMID:25616665; http://dx.doi.org/ 10.1074/jbc.M114.620252 · DOI · Paper page
  39. Wang H, Zhu LJ, Yang YC, Wang ZX, Wang R. MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating G(1)/S transition and apoptosis by targeting p21 (WAF1/CIP1). Br J Cancer 2014; 111:339-54; PMID:24921914; http://dx.doi.org/10.1038/bjc.2014.157 · DOI
  40. Elhanati S, Kanfi Y, Varvak A, Roichman A, Carmel-Gross I, Barth S, Gibor G, Cohen HY. Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep 2013; 4:905-12; PMID:24012758; http://dx.doi.org/ 10.1016/j.celrep.2013.08.006 · DOI
  41. Kawahara TL, Rapicavoli NA, Wu AR, Qu K, Quake SR, Chang HY. Dynamic chromatin localization of Sirt6 shapes stress-and aging- related transcriptional networks. PLoS Genet 2011; 7:e1002153; PMID:21738489; http://dx.doi.org/10.1371/journal.pgen.1002153 · DOI

Cited by

Sorted by citations

Authors
Xu, S., Huang, H., Chen, Y.-N., Deng, Y.-T., Zhang, B., Xiong, X.-D., Yuan, Y., Zhu, Y., Huang, H., Xie, L., & Liu, X.
Affiliations
  • Guangdong Medical College (CN)
  • Institute of Aging Research, Guangdong Medical University, Dongguan, P.R. China
Corresponding author
Liu, Xinguang
ORCID
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2016-09-15
Volume
15
Issue
21
Pages
2920-2930
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.1080/15384101.2016.1224043
PMC
PMC5105918
OpenAlex
W2512633620
Cited by
59
References
2
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 10 · 2022: 4 · 2021: 14 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 1
FWCI
2.22
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (A2015288, 81370456, 2014A030310027, 2016A030313684, B2013002, 81170327, 9252402301000002)
  • Natural Science Foundation of Guangdong Province (81170327, 9252402301000002, B2013002, 2016A030313684, 81370456, 2014A030310027, A2015288)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
cisplatin resistance, lung cancer, DNA damage response, p21, A549 cells, A549/DDP cells, γH2AX, G1/S checkpoint, microRNA, chemoresistance
MeSH terms
A549 Cells, Base Sequence, Cell Survival, Cisplatin, DNA Damage, DNA Repair, Humans, Lung Neoplasms, Down-Regulation, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Gene Expression Profiling, MicroRNAs, Cyclin-Dependent Kinase Inhibitor p21, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review