Advertisement

Clinical and Translational Oncology

, Volume 20, Issue 4, pp 457–466 | Cite as

miR-33a inhibits cell proliferation and invasion by targeting CAND1 in lung cancer

  • M. Kang
  • Y. Li
  • Y. Zhao
  • S. He
  • J. Shi
Research Article

Abstract

Background

Lung cancer continues to be one of the top five causes of cancer-related mortality. This study aims to identify down- and upregulated miRNAs and mRNA which can be used as potential biomarkers and/or therapeutic targets for lung cancer.

Methods

Integrated analysis of differential expression profiles of miRNA and mRNA in lung cancer was performed by searching Gene Expression Omnibus datasets. Based on miRNA expression profiles, direct mRNA targets of miRNAs with experimental support were identified through miRTarBase. The levels of representative miRNAs and mRNAs were confirmed through qualitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).

Results

The miR-33a was decreased in non-small cell lung cancer (NSCLC) tissues compared with the para-carcinoma tissues, whereas its target mRNA of cullin-associated NEDD8-dissociated protein 1 (CAND1) was increased in NSCLC tissues. Further research has shown that miR-33a can inhibit lung cancer cell proliferation, cell cycle progression, and migration by targeting CAND1. Moreover, the CAND1 knockout lung cancer cells showed similar results as cells transfected with miR-33a mimic.

Conclusions

These results suggested that the data mining based on online databases was an effective method in finding novel target in cancer research, and the miR-33a and CAND1 played an important role in lung cancer proliferation and cell migration.

Keywords

Lung cancer Data mining miR-33a CAND1 

Notes

Funding

This work was supported by the Guilin Science and Technology Project (Project Number: 20150126-1-2).

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest in the study.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Esposito L, Conti D, Ailavajhala R, Khalil N, Giordano A. Lung cancer: are we up to the challenge? Curr Genom. 2010;11(7):513.CrossRefGoogle Scholar
  2. 2.
    Granville CA, Dennis PA. An overview of lung cancer genomics and proteomics. Am J Respir Cell Mol Biol. 2005;32(3):169.CrossRefPubMedGoogle Scholar
  3. 3.
    Wang Y, Wen L, Zhao SH, Ai ZH, Guo JZ, Liu WC. FoxM1 expression is significantly associated with cisplatin-based chemotherapy resistance and poor prognosis in advanced non-small cell lung cancer patients. Lung cancer. 2013;79(2):173.CrossRefPubMedGoogle Scholar
  4. 4.
    Yokota J, Kohno T. Molecular footprints of human lung cancer progression. Cancer Sci. 2004;95(3):197.CrossRefPubMedGoogle Scholar
  5. 5.
    Cui M, Augert A, Rongione M, Conkrite K, Parazzoli S, Nikitin AY, et al. PTEN is a potent suppressor of small cell lung cancer. Mol Cancer Res. 2014;12(5):654.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001;2(12):919.CrossRefPubMedGoogle Scholar
  7. 7.
    Tutar Y, Ozgur A, Tutar E, Tutar L, Pulliero A, Izzotti A. Regulation of oncogenic genes by MicroRNAs and pseudogenes in human lung cancer. Biomed Pharmacother = Biomedecine & pharmacotherapie. 2016;83:1182.CrossRefGoogle Scholar
  8. 8.
    Markou A, Sourvinou I, Vorkas PA, Yousef GM, Lianidou E. Clinical evaluation of microRNA expression profiling in non small cell lung cancer. Lung cancer. 2013;81(3):388.CrossRefPubMedGoogle Scholar
  9. 9.
    Tang D, Shen Y, Wang M, Yang R, Wang Z, Sui A, et al. Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur J Cancer Prev. 2013;22(6):540.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhu W, Zhou K, Zha Y, Chen D, He J, Ma H, et al. Diagnostic value of serum miR-182, miR-183, miR-210, and miR-126 levels in patients with early-stage non-small cell lung cancer. PLoS One. 2016;11(4):e0153046.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Li G, Li M, Hu J, Lei R, Xiong H, Ji H, et al. The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis. Oncogene. 2016;36(7):989–98.CrossRefPubMedGoogle Scholar
  12. 12.
    Chiu KL, Kuo TT, Kuok QY, Lin YS, Hua CH, Lin CY, et al. ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis. Sci Rep. 2015;5:16426.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402.CrossRefPubMedGoogle Scholar
  14. 14.
    Xiao H, Zeng J, Li H, Chen K, Yu G, Hu J, et al. MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis. Oncotarget. 2015;6(15):13201.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Green CM, Erdjument-Bromage H, Tempst P, Lowndes NF. A novel Rad24 checkpoint protein complex closely related to replication factor C. Curr Biol. 2000;10(1):39.CrossRefPubMedGoogle Scholar
  16. 16.
    Banerjee J, Pradhan R, Gupta A, Kumar R, Sahu V, Upadhyay AD, et al. CDK4 in lung, and head and neck cancers in old age: evaluation as a biomarker. Clin Trans Oncol. 2017;19(5):571–8.CrossRefGoogle Scholar
  17. 17.
    Kim H, Shin EA, Kim CG, Lee DY, Kim B, Baek NI, et al. Obovatol induces apoptosis in non-small cell lung cancer cells via C/EBP homologous protein activation. Phytother Res. 2016;30(11):1841.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang L, Li L, Wei H, Guo L, Ai C, Xu H, et al. Transcriptional factor FOXO3 negatively regulates the expression of nm23-H1 in non-small cell lung cancer. Thoracic Cancer. 2016;7(1):9.CrossRefPubMedGoogle Scholar
  19. 19.
    Han SY, Han HB, Tian XY, Sun H, Xue D, Zhao C, et al. MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma. Oncotarget. 2016;7(27):42461.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Wei Q, Lei R, Hu G. Roles of miR-182 in sensory organ development and cancer. Thoracic Cancer. 2015;6(1):2.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    VanArsdale T, Boshoff C, Arndt KT, Abraham RT. Molecular pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. Clin Can Res. 2015;21(13):2905.CrossRefGoogle Scholar
  22. 22.
    Pore MM, Hiltermann TJ, Kruyt FA. Targeting apoptosis pathways in lung cancer. Cancer Lett. 2013;332(2):359.CrossRefPubMedGoogle Scholar
  23. 23.
    Korzeniewski N, Hohenfellner M, Duensing S. CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. Neoplasia. 2012;14(9):799.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chua YS, Boh BK, Ponyeam W, Hagen T. Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo. PLoS One. 2011;6(1):e16071.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Zhang M, Gong W, Zuo B, Chu B, Tang Z, Zhang Y, et al. The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer. Oncotarget. 2016;7(48):78640.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Guo XF, Wang AY, Liu J. HIFs-MiR-33a-Twsit1 axis can regulate invasiveness of hepatocellular cancer cells. Eur Rev Med Pharmacol Sci. 2016;20(14):3011.PubMedGoogle Scholar
  27. 27.
    Zheng D, Haddadin S, Wang Y, Gu LQ, Perry MC, Freter CE, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol. 2011;4(6):575.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Abd-El-Fattah AA, Sadik NA, Shaker OG, Aboulftouh ML. Differential microRNAs expression in serum of patients with lung cancer, pulmonary tuberculosis, and pneumonia. Cell Biochem Biophys. 2013;67(3):875.CrossRefPubMedGoogle Scholar
  29. 29.
    Dubiel D, Gierisch ME, Huang X, Dubiel W, Naumann M. CAND1-dependent control of cullin 1-RING Ub ligases is essential for adipogenesis. Biochem Biophys Acta. 2013;1833(5):1078.CrossRefPubMedGoogle Scholar
  30. 30.
    Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI. Altered cJUN expression: an early event in human lung carcinogenesis. Can Res. 1996;56(2):305.Google Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2017

Authors and Affiliations

  1. 1.Department of Medical OncologyThe Affiliated Hospital of Guilin Medical CollegeGuilinChina

Personalised recommendations