Biotechnology Letters

, Volume 39, Issue 11, pp 1621–1629 | Cite as

miR-93 enhances hepatocellular carcinoma invasion and metastasis by EMT via targeting PDCD4

  • Chunmei Ji
  • Hang Liu
  • Qiang Yin
  • Hui Li
  • Han GaoEmail author
Original Research Paper



To clarify the potential biological function of miR-93 and its related molecular mechanism underlying metastasis in human hepatocellular carcinoma (HCC).


miR-93 was significantly up-regulated in HCC tissues and was associated with poor 5-year overall survival in HCC patients. Transwell assays showed that over-expression of miR-93 increased HCC cell migration and invasion in vitro. Programmed cell death 4 (PDCD4) was a target gene of miR-93 and miR-93 could down-regulate the expression of PDCD4 by directly targeting its 3′-UTR. The re-expression of PDCD4 could attenuate the HCC cell invasion and migration induced by miR-93, while the knockdown of PDCD4 would promote HCC cell migration and invasion via the epithelial-mesenchymal transition (EMT) pathway.


miR-93 provides new insight into the molecular mechanisms of pathogenesis and progression in HCC and offer a potential therapeutic target for the treatment of HCC patients.


Epithelial-mesenchymal transition (EMT) pathway Hepatocellular carcinoma Liver cancer metastasis miR-93 PDCD4 




Compliance with ethical standards

Conflicts of interest



  1. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233CrossRefPubMedPubMedCentralGoogle Scholar
  2. Chu KK, Cheung TT (2015) Update in management of hepatocellular carcinoma in Eastern population. World J Hepatol 7:1562–1571CrossRefPubMedPubMedCentralGoogle Scholar
  3. Chung KY et al (2011) Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition. Hepatology 54:307–318CrossRefPubMedGoogle Scholar
  4. Fornari F et al (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27:5651–5661CrossRefPubMedGoogle Scholar
  5. Guo PT, Yang D, Sun Z, Xu HM (2013) PDCD4 functions as a suppressor for pT2a and pT2b stage gastric cancer. Oncol Rep 29:1007–1012CrossRefPubMedGoogle Scholar
  6. Kulik LM, Chokechanachaisakul A (2015) Evaluation and management of hepatocellular carcinoma. Clin Liver Dis 19:23–43CrossRefPubMedGoogle Scholar
  7. Kumar S, Das A, Sen S (2014) Extracellular matrix density promotes EMT by weakening cell-cell adhesions. Mol BioSyst 10:838–850CrossRefPubMedGoogle Scholar
  8. Li JZ et al (2016) The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis. Chin J Cancer 35:95CrossRefPubMedPubMedCentralGoogle Scholar
  9. Liang H et al (2016) miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma. Sci Rep 6:23772CrossRefPubMedPubMedCentralGoogle Scholar
  10. Negrini M, Nicoloso MS, Calin GA (2009) MicroRNAs and cancer–new paradigms in molecular oncology. Curr Opin Cell Biol 21:470–479CrossRefPubMedGoogle Scholar
  11. Ohta K et al (2015) MicroRNA-93 activates c-Met/PI3 K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget 6:3211–3224CrossRefPubMedGoogle Scholar
  12. Tan G et al (2016) MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-kappaB signaling pathway. Sci Rep 6:22328CrossRefPubMedPubMedCentralGoogle Scholar
  13. Wang Q et al (2013) Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice. Eur J Cancer 49:1761–1770CrossRefPubMedPubMedCentralGoogle Scholar
  14. Wei R et al (2013) Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma. Clin Cancer Res 19:4780–4791CrossRefPubMedGoogle Scholar
  15. Xiao S et al (2016) Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition. Hepatology 63:1256–1271CrossRefPubMedPubMedCentralGoogle Scholar
  16. Zhang H et al (2006) Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Oncogene 25:6101–6112CrossRefPubMedGoogle Scholar
  17. Zhang X et al (2014) F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated by miR-17 and miR-20a. Oncotarget 5:6178–6190CrossRefPubMedPubMedCentralGoogle Scholar
  18. Zhou X et al (2015) miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma. Oncogene 34:965–977CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Chunmei Ji
    • 1
  • Hang Liu
    • 2
  • Qiang Yin
    • 3
  • Hui Li
    • 4
  • Han Gao
    • 5
    Email author
  1. 1.Department of Clinical LaboratoryPeople’s Hospital of WeifangWeifangPeople’s Republic of China
  2. 2.Department of Interventional TherapyYidu Central Hospital of WeifangWeifangPeople’s Republic of China
  3. 3.Department of OncologyPeople‘s Hospital of RizhaoRizhaoPeople’s Republic of China
  4. 4.Department of PIVASPeople’s Hospital of ZhangqiuJinanPeople’s Republic of China
  5. 5.Department of PathologyQingdao Municipal HospitalQingdaoPeople’s Republic of China

Personalised recommendations