DOI QR코드

DOI QR Code

MiR-421 Regulates Apoptosis of BGC-823 Gastric Cancer Cells by Targeting Caspase-3

  • Wu, Jian-Hong (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Yao, Yong-Liang (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Gu, Tao (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Wang, Ze-You (Institute of Cancer Research, Central South University) ;
  • Pu, Xiong-Yong (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Sun, Wang-Wei (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Zhang, Xian (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Jiang, Yi-Biao (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University) ;
  • Wang, Jian-Jun (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University)
  • Published : 2014.07.15

Abstract

MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.

Keywords

References

  1. Ali Z, Deng Y and Ma C (2012). Progress of research in gastric cancer. J Nanosci Nanotechnol, 12, 8241-8. https://doi.org/10.1166/jnn.2012.6692
  2. Bartel DP (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215-33. https://doi.org/10.1016/j.cell.2009.01.002
  3. Brennecke J, Stark A, Russell RB, et al (2005). Principles of microRNA-target recognition. PLoS Biol, 3, 85. https://doi.org/10.1371/journal.pbio.0030085
  4. Chen L, Tang Y, Wang J, et al (2013). MiR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4. Biochem Biophys Res Commun, 435, 745-50. https://doi.org/10.1016/j.bbrc.2013.05.056
  5. Du L, Pertsemlidis A (2012). MicroRNA regulation of cell viability and drug sensitivity in lung cancer. Expert Opin Biol Ther, 12, 1221-39. https://doi.org/10.1517/14712598.2012.697149
  6. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  7. Guo J, Miao Y, Xiao B, et al (2009). Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol, 24, 652-7. https://doi.org/10.1111/j.1440-1746.2008.05666.x
  8. He L, Hannon GJ (2004). MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet, 5, 522-31. https://doi.org/10.1038/nrg1379
  9. Hoshi T, Sasano H, Kato K, et al (1998). Immunohlstochemistry of Caspase-3/cpp32 in human stomach and its correlation with ceil proliferation and apoptosis. Anticancer Res, 18, 4347-53.
  10. Hsu KW, Hsieh RH, Huang KH, et al (2012). Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis, 33, 1459-67. https://doi.org/10.1093/carcin/bgs165
  11. Hu H, Du L, Nagabayashi G, et al (2010). ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci USA, 107, 1506-11. https://doi.org/10.1073/pnas.0907763107
  12. Hu YR, Liu SQ, Tian YX, et al (2009). Effects of a disintegrin, adinbitor, from gloydius blomhoffi brevicaudus on Akt signal pathway and proliferation, migration and apoptosis of SSMC7721 cells. Zhong Guo Sheng Wu Hua Xue Yu Fen Zi ShengWu Xue Bao, 25, 662-8.
  13. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  14. Kania J, Konturek SJ, Marlicz K, et al (2003). Expression of survivin and caspase-3 in gastric cancer. Dig Dis Sci, 48, 266-71. https://doi.org/10.1023/A:1021915124064
  15. Kim K, Chun KH, Suh PG et al (2011). Alterations in cell proliferation related gene expressions in gastric cancer. Crit Rev Eukaryot Gene Expr, 21, 237-54. https://doi.org/10.1615/CritRevEukarGeneExpr.v21.i3.20
  16. Kong D, Piao YS, Yamashita S, et al (2012). Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells. Oncogene, 31, 3949-60. https://doi.org/10.1038/onc.2011.558
  17. Konishi H, Ichikawa D, Komatsu S, et al (2012). Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br J Cancer, 106, 740-7. https://doi.org/10.1038/bjc.2011.588
  18. Krajewska M, Wang HG, Krajewski S, et al (1997). Immunohistochemical analysis of in vivo patterns of expression of CPP32 (caspase-3), a cell death protease. Cancer Res, 57, 1605-11.
  19. Lee S, Vasudevan S (2013). Post-transcriptional stimulation of gene expression by microRNAs. Adv Exp Med Biol, 768, 97-126. https://doi.org/10.1007/978-1-4614-5107-5_7
  20. Liu H (2009). MicroRNAs in breast cancer initiation and progression. Cell Mol Life Sci, 69, 3587-99.
  21. Liu XX, Li XJ, Zhang B, et al (2011). MicroRNA-26b is underexpressed in human breast cancer and induces cell apoptosis by targeting SLC7A11. FEBS Lett, 585, 1363-7. https://doi.org/10.1016/j.febslet.2011.04.018
  22. Menendez P, Villarejo P, Padilla D, et al (2013). Diagnostic and prognostic significance of serum microRNAs in colorectal cancer. J Surg Oncol, 107, 217-20. https://doi.org/10.1002/jso.23245
  23. Oshima H, Ishikawa T, Yoshida GJ, et al (2013). TNF-$\alpha$/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells. Oncogene, 356, [Epub ahead of print].
  24. Oulas A, Boutla A, Gkirtzou K, et al (2009). Prediction of novel microRNA genes in cancerassociated genomic regions.a combined computational and experimental approach. Nucleic Acids Res, 37, 3276-87. https://doi.org/10.1093/nar/gkp120
  25. Peng S, Zeng X, Li X, et al (2009). Multi-class cancer classification through gene expression profiles: microRNA versus Mrna. J Genet Genomics, 36, 409-16. https://doi.org/10.1016/S1673-8527(08)60130-7
  26. Peralta-Zaragoza O, Bermudez-Morales VH, Madrid.Marina V (2010). RNA interference: biogenesis molecular mechanisms and its applications in cervical cancer. Rev Invest Clin, 62, 63-80.
  27. Saeki N, Ono H, Sakamoto H et al (2013). Genetic factors related to gastric cancer susceptibility identified using a genomewide association study. Cancer Sci, 104, 1-8. https://doi.org/10.1111/cas.12042
  28. Samali A, Cai J, Zhivotovsky B, et al (1999). Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. EMBO J, 18, 2040-8. https://doi.org/10.1093/emboj/18.8.2040
  29. Segura MF, Greenwald HS, Hanniford D, et al (2012). MicroRNA and cutaneous melanoma: from discovery to prognosis and therapy. Carcinogenesis, 33, 1823-32. https://doi.org/10.1093/carcin/bgs205
  30. Tang G, Tang X (2013). Short tandem target mimic: a long journey to the engineered molecular landmine for selective destruction/blockage of microRNAs in plants and animals. J Genet Genomics, 40, 291-6. https://doi.org/10.1016/j.jgg.2013.02.004
  31. Thiel A, Ristimaki A (2012). Gastric cancer: basic aspects. Helicobacter, 1, 26-9.
  32. Wei MC, Zong WX, Cheng EH, et al (2011). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science, 292, 727-30.
  33. Xiao LJ, Zhao S, Zhao EH, et al (2013). Clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 expression in gastric carcinomas. Oncol Lett, 6, 1277-84. https://doi.org/10.3892/ol.2013.1532
  34. Xu L, Dai WQ, Xu XF, et al (2012). Effects of Multiple-target anti-microRNA antisense oligodeoxyribonucleotides on proliferation and migration of gastric cancer cells. Asian Pac J Cancer Prev, 13, 3203-7. https://doi.org/10.7314/APJCP.2012.13.7.3203
  35. Yang L (2006). Incidence and mortality of gastric cancer in China. World J Gastroenterol, 12, 17-20. https://doi.org/10.3748/wjg.v12.i1.17
  36. Yao YL, Wu XY, Wu JH, et al (2013). Effects of microRNA-106 on proliferation of gastric cancer cell through regulating p21 and E2F5. Asian Pac J Cancer Prev, 14, 2839-43. https://doi.org/10.7314/APJCP.2013.14.5.2839
  37. Yu JW, Wu JG, Zheng LH, et al (2009). Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma. J Exp Clin Cancer Res, 28, 55. https://doi.org/10.1186/1756-9966-28-55

Cited by

  1. Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer vol.15, pp.20, 2014, https://doi.org/10.7314/APJCP.2014.15.20.8893
  2. Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation vol.16, pp.10, 2015, https://doi.org/10.7314/APJCP.2015.16.10.4203
  3. MicroRNAs May Serve as Emerging Molecular Biomarkers for Diagnosis and Prognostic Assessment or as Targets for Therapy in Gastric Cancer vol.16, pp.12, 2015, https://doi.org/10.7314/APJCP.2015.16.12.4813
  4. MicroRNA-455 inhibits proliferation and invasion of colorectal cancer by targeting RAF proto-oncogene serine/threonine-protein kinase vol.36, pp.2, 2015, https://doi.org/10.1007/s13277-014-2766-3
  5. MicroRNA‑133b inhibits cell migration and invasion by targeting matrix metalloproteinase 14 in glioblastoma pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3657
  6. AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro vol.178, pp.5, 2016, https://doi.org/10.1007/s12010-015-1925-3
  7. Major apoptotic mechanisms and genes involved in apoptosis vol.37, pp.7, 2016, https://doi.org/10.1007/s13277-016-5035-9
  8. miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma vol.37, pp.7, 2016, https://doi.org/10.1007/s13277-015-4578-5
  9. In vivo and in vitro effects of microRNA-124 on human gastric cancer by targeting JAG1 through the Notch signaling pathway pp.07302312, 2017, https://doi.org/10.1002/jcb.26413
  10. MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11 vol.14, pp.3, 2017, https://doi.org/10.3892/etm.2017.4798
  11. Inhibitor of growth 3 induces cell death by regulating cell proliferation, apoptosis and cell cycle arrest by blocking the PI3K/AKT pathway vol.25, pp.9-10, 2018, https://doi.org/10.1038/s41417-018-0023-4
  12. Alterations of MicroRNA Expression in the Liver, Heart, and Testis of Mice Upon Exposure to Repeated Low-Dose Radiation vol.16, pp.3, 2018, https://doi.org/10.1177/1559325818799561
  13. MicroRNA-421 suppresses the apoptosis and autophagy of hippocampal neurons in epilepsy mice model by inhibition of the TLR/MYD88 pathway vol.233, pp.9, 2018, https://doi.org/10.1002/jcp.26498