Skip to main content
SpringerLink
Log in

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

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Objectives

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

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu KK, Cheung TT (2015) Update in management of hepatocellular carcinoma in Eastern population. World J Hepatol 7:1562–1571

    Article  PubMed  PubMed Central  Google Scholar 

  • Chung KY et al (2011) Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition. Hepatology 54:307–318

    Article  CAS  PubMed  Google Scholar 

  • Fornari F et al (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27:5651–5661

    Article  CAS  PubMed  Google Scholar 

  • Guo PT, Yang D, Sun Z, Xu HM (2013) PDCD4 functions as a suppressor for pT2a and pT2b stage gastric cancer. Oncol Rep 29:1007–1012

    Article  CAS  PubMed  Google Scholar 

  • Kulik LM, Chokechanachaisakul A (2015) Evaluation and management of hepatocellular carcinoma. Clin Liver Dis 19:23–43

    Article  PubMed  Google Scholar 

  • Kumar S, Das A, Sen S (2014) Extracellular matrix density promotes EMT by weakening cell-cell adhesions. Mol BioSyst 10:838–850

    Article  CAS  PubMed  Google Scholar 

  • 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 35:95

    Article  PubMed  PubMed Central  Google Scholar 

  • Liang H et al (2016) miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma. Sci Rep 6:23772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negrini M, Nicoloso MS, Calin GA (2009) MicroRNAs and cancer–new paradigms in molecular oncology. Curr Opin Cell Biol 21:470–479

    Article  CAS  PubMed  Google Scholar 

  • 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 6:3211–3224

    Article  PubMed  Google Scholar 

  • Tan G et al (2016) MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-kappaB signaling pathway. Sci Rep 6:22328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 49:1761–1770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei R et al (2013) Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma. Clin Cancer Res 19:4780–4791

    Article  CAS  PubMed  Google Scholar 

  • Xiao S et al (2016) Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition. Hepatology 63:1256–1271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H et al (2006) Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Oncogene 25:6101–6112

    Article  CAS  PubMed  Google Scholar 

  • 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 5:6178–6190

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou X et al (2015) miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma. Oncogene 34:965–977

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, People’s Hospital of Weifang, Weifang, Shandong, People’s Republic of China

    Chunmei Ji

  2. Department of Interventional Therapy, Yidu Central Hospital of Weifang, Weifang, Shandong, People’s Republic of China

    Hang Liu

  3. Department of Oncology, People‘s Hospital of Rizhao, Rizhao, Shandong, People’s Republic of China

    Qiang Yin

  4. Department of PIVAS, People’s Hospital of Zhangqiu, Jinan, Shandong, People’s Republic of China

    Hui Li

  5. Department of Pathology, Qingdao Municipal Hospital, No. 1 Jiaozhou Road, Shibei District, Qingdao, 266000, Shandong, People’s Republic of China

    Han Gao

Authors
  1. Chunmei Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiang Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Han Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Han Gao.

Ethics declarations

Conflicts of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ji, C., Liu, H., Yin, Q. et al. miR-93 enhances hepatocellular carcinoma invasion and metastasis by EMT via targeting PDCD4. Biotechnol Lett 39, 1621–1629 (2017). https://doi.org/10.1007/s10529-017-2403-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-017-2403-5

Keywords

Search

Navigation