Tumor Biology

, Volume 37, Issue 8, pp 10507–10515 | Cite as

The effect of antisense inhibitor of miRNA 106b∼25 on the proliferation, invasion, migration, and apoptosis of gastric cancer cell

Original Article

Abstract

Accumulating data has demonstrated that miRNA 106b∼25, which are composed of the highly conserved miRNA 106b, miRNA 93, and miRNA 25, play carcinogenic roles in cancers. We investigated the expression of miRNA 106b∼25 in gastric cancer cells (SGC 7901, MGC 803, BGC 823) and normal gastric epithelial cell then inhibited miRNA 106b∼25 expression via transiently transfecting their antisense inhibitor. After miRNA 106b∼25 cluster was inhibited, MTT, Scratch test, Transwell invasion test, and flow cytometry were applied to investigate the proliferation, invasion, migration, cell cycle, and apoptosis of gastric cancer cell. The expression of miRNA 106b, miRNA 93, and miRNA 25 in gastric cancer cells SGC 7901, MGC 803, and BGC 823 was significantly higher than in gastric epithelial cell GES-1. The most significant suppression of miRNA 106b∼25 expressions can be detected in MGC 803 cell after transiently transfecting their antisense inhibitors. So, MGC 803 cell was selected as our research object. After inhibiting miRNA 106b and miRNA 93 respectively and combined, the proliferation, migration, and invasion of gastric cancer cell MGC 803 were significantly suppressed. The most significant suppression was observed in combined inhibiting group. After miRNA 106b∼25 cluster was inhibited respectively or combined, more gastric cancer cells were arrested in the G0G1 phase. However, there was no statistical difference in comparing with control groups. While the percentages of apoptotic cells increased after miRNA 106b∼25 cluster was inhibited, the statistical difference was detected only in combined inhibiting group. Inhibiting miRNA 106b∼25 cluster via transfecting antisense inhibitor can influence biological behavior of gastric cancer cell.

Keywords

miRNA 106b miRNA 93 miRNA 25 Antisense inhibitors Gastric cancer Biological behavior 

Notes

Acknowledgments

This work was supported by the Tianjin Natural Science Funds (No. 13JCYBJC24200), Tianjin Medical University Natural Science Funds (2013KY02), and National Natural Science Fund of China (81502309).

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Zeng Y. Principles of micro-RNA production and maturation. Oncogene. 2006;25:6156–62.CrossRefPubMedGoogle Scholar
  2. 2.
    Bueno MJ, Perez DCI, Malumbres M. Control of cell proliferation pathways by microRNAs. Cell Cycle. 2008;7:3143–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer. 2011;47:1127–37.CrossRefPubMedGoogle Scholar
  4. 4.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Kato M, Slack FJ. microRNAs: small molecules with big roles—C. elegans to human cancer. Biol Cell. 2008;100:71–81.CrossRefPubMedGoogle Scholar
  6. 6.
    Tong F, Cao P, Yin Y, Xia S, Lai R, Liu S. MicroRNAs in gastric cancer: from benchtop to bedside. Dig Dis Sci. 2014;59:24–30.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhu Y, Jiang Q, Lou X, Ji X, Wen Z, Wu J, et al. MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells. PLoS One. 2012;7:e35147.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cai K, Wang Y, Bao X. MiR-106b promotes cell proliferation via targeting RB in laryngeal carcinoma. J Exp Clin Cancer Res. 2011;30:73.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu Y, Zhang Y, Wen J, Liu L, Zhai X, Liu J, et al. A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma. PLoS One. 2012;7:e32230.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRefPubMedGoogle Scholar
  11. 11.
    Petrocca F, Vecchione A, Croce CM. Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Choi N, Park J, Lee JS, Yoe J, Park GY, Kim E, et al. miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget. 2015;6:23533–47.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gong C, Qu S, Liu B, Pan S, Jiao Y, Nie Y, et al. MiR-106b expression determines the proliferation paradox of TGF-beta in breast cancer cells. Oncogene. 2015;34:84–93.CrossRefPubMedGoogle Scholar
  14. 14.
    Zheng L, Zhang Y, Liu Y, Zhou M, Lu Y, Yuan L, et al. MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer. J Transl Med. 2015;13:252.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, Hobbs RM, et al. Identification of the miR-106b∼25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal. 2010;3:a29.CrossRefGoogle Scholar
  16. 16.
    Tamura G. Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol. 2006;12:192–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D, et al. Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol. 2009;24:652–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang R, Wang W, Li F, Zhang H, Liu J. MicroRNA-106b∼25 expressions in tumor tissues and plasma of patients with gastric cancers. Med Oncol. 2014;31:243.CrossRefPubMedGoogle Scholar
  19. 19.
    Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011;30:806–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Fang L, Du WW, Yang W, Rutnam ZJ, Peng C, Li H, et al. MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell Cycle. 2012;11:4352–65.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, et al. The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. Gastroenterology. 2009;136:1689–700.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, et al. Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 2009;37:1672–81.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chen HZ, Tsai SY, Leone G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer. 2009;9:785–97.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    DeGregori J. The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta. 2002;1602:131–50.PubMedGoogle Scholar
  25. 25.
    Lazzerini DE, Helin K. E2F1 is crucial for E2F-dependent apoptosis. EMBO Rep. 2005;6:661–8.CrossRefGoogle Scholar
  26. 26.
    Gupta S, Read DE, Deepti A, Cawley K, Gupta A, Oommen D, et al. Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis. 2012;3:e333.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhao ZN, Bai JX, Zhou Q, Yan B, Qin WW, Jia LT, et al. TSA suppresses miR-106b-93-25 cluster expression through downregulation of MYC and inhibits proliferation and induces apoptosis in human EMC. PLoS One. 2012;7:e45133.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wan X, Ding X, Chen S, Song H, Jiang H, Fang Y, et al. The functional sites of miRNAs and lncRNAs in gastric carcinogenesis. Tumour Biol. 2015;36:521–32.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Gastric Cancer SurgeryTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjinChina
  2. 2.Department of Cancer Prevention CenterTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjinChina
  3. 3.Tianjin Medical University Cancer Institute and HospitalTianjinChina

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