Medical Oncology

, Volume 29, Issue 2, pp 886–892 | Cite as

MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis

  • Zhibo Hou
  • Li Xie
  • Lixia Yu
  • Xiaoping Qian
  • Baorui LiuEmail author
Original Paper


Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in development and progression in various types of cancers, but its role in gastric cancer has not been fully elucidated. The purpose of this study was to investigate the levels of miR-146a expression and its function in human gastric cancer. Quantitative real-time polymerase chain reaction was used to detect the levels of miR-146a expression in gastric cancer tissue samples and cell lines. The cell growth rate of MKN-45 gastric cancer cells transfected with miR-146a mimics was examined by MTT assay. The effects of miR-146a on cell cycle and apoptosis were assessed by FACS analyses in MKN-45 cells. Thirty-six of 43 gastric cancer tissue samples (84%) showed decreased expression of miR-146a. We found low expression of miR-146a was correlated with increased tumor size (P = 0.006) and poor differentiation (P = 0.010) in gastric cancer. Overall survival time of patients with high miR-146a expression was significantly longer than that of patients with low expression of miR-146a (P = 0.011). The MTT assay showed that introduction of miR-146a inhibited cell proliferation in MKN-45 cells (P < 0.05). The proportion of apoptotic cells induced by transfection of miR-146a mimics were greater than that induced by transfection of the negative control mimics (11.9 vs. 5.9%). Our results suggested that miR-146a has potential as a novel suppressor gene in gastric cancer and its down-regulation may promote the progression of gastric cancer.


Gastric cancer MiR-146a Clinicopathological features Prognosis Apoptosis 







Quantitative real-time polymerase chain reaction


Formaldehyde-fixed, paraffin-embedded


3-(4, 5-Dimethylthiazol-2-yl)-2, 4-diphenyl-tetrazolium bromide



This work was supported by the National Natural Science Foundation of China (No. 81071815), Jiangsu Province Key Medical Cent Foundation and Scientific and Technological Innovation Plan Fund of Postgraduate from Jiangsu Province (No. 5X22013084).


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, Wu KC, Wu DC, Sollano J, Kachintorn U, Gotoda T, Lin JT, You WC, Ng EK, Sung JJ. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87.PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMedGoogle Scholar
  5. 5.
    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.PubMedGoogle Scholar
  6. 6.
    Wu WK, Cho CH, Lee CW, Fan D, Wu K, Yu J, Sung JJ. Dysregulation of cellular signaling in gastric cancer. Cancer Lett. 2010;295:144–53.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP. The widespread impact of mammalian micrornas on mrna repression and evolution. Science. 2005;310:1817–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Ambros V. The functions of animal micrornas. Nature. 2004;431:350–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Esquela-Kerscher A, Slack FJ. Oncomirs—micrornas with a role in cancer. Nat Rev Cancer. 2006;6:259–69.PubMedCrossRefGoogle Scholar
  11. 11.
    Croce CM. Causes and consequences of microrna dysregulation in cancer. Nat Rev Genet. 2009;10:704–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Xie L, Qian X, Liu B. Micrornas: novel biomarkers for gastrointestinal carcinomas. Mol Cell Biochem. 2010;341:291–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Shen R, Pan S, Qi S, Lin X, Cheng S. Epigenetic repression of microrna-129–2 leads to overexpression of sox4 in gastric cancer. Biochem Biophys Res Commun. 2010;394:1047–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Li L, Chen XP, Li YJ. Microrna-146a and human disease. Scand J Immunol. 2010;71:227–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH. Mir-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 2010;70:1486–95.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM. Aberrant expression of oncogenic and tumor-suppressive micrornas in cervical cancer is required for cancer cell growth. PLoS One. 2008;3:e2557.PubMedCrossRefGoogle Scholar
  17. 17.
    Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC. Expression of microrna-146 suppresses nf-kappab activity with reduction of metastatic potential in breast cancer cells. Oncogene. 2008;27:5643–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Pacifico F, Crescenzi E, Mellone S, Iannetti A, Porrino N, Liguoro D, Moscato F, Grieco M, Formisano S, Leonardi A. Nuclear factor-{kappa}b contributes to anaplastic thyroid carcinomas through up-regulation of mir-146a. J Clin Endocrinol Metab. 2010;95:1421–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 2008;14:417–24.PubMedCrossRefGoogle Scholar
  20. 20.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common snp in pre-mir-146a decreases mature mir expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2008;105:7269–74.PubMedCrossRefGoogle Scholar
  21. 21.
    Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 up-regulates mir-146, which suppresses breast cancer metastasis. Cancer Res. 2009;69:1279–83.PubMedCrossRefGoogle Scholar
  22. 22.
    Tchernitsa O, Kasajima A, Schafer R, Kuban RJ, Ungethum U, Gyorffy B, Neumann U, Simon E, Weichert W, Ebert MP, Rocken C. Systematic evaluation of the mirna-ome and its downstream effects on mrna expression identifies gastric cancer progression. J Pathol. 2010;222:310–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Boominathan L. The guardians of the genome (p53, ta-p73, and ta-p63) are regulators of tumor suppressor mirnas network. Cancer Metastasis Rev. 2010;29:613–39.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zhibo Hou
    • 1
    • 2
  • Li Xie
    • 2
  • Lixia Yu
    • 2
  • Xiaoping Qian
    • 2
  • Baorui Liu
    • 1
    • 2
    Email author
  1. 1.The Comprehensive Cancer Center of Drum Tower HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.The Comprehensive Cancer Center of Drum Tower HospitalMedical School of Nanjing UniversityNanjingPeople’s Republic of China

Personalised recommendations