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Tumor Biology

, Volume 36, Issue 11, pp 8455–8463 | Cite as

Effects of sorafenib on lung metastasis in rats with hepatocellular carcinoma: the role of microRNAs

  • Yi Shi
  • Aimin Huang
Research Article

Abstract

Many patients with advanced hepatocellular carcinoma (HCC) develop lung metastasis and available treatments are limited. The anticancer drug sorafenib has opened a window of hope for patients with advanced hepatocellular carcinoma. However, the effect of sorafenib is limited by drug resistance. MicroRNAs have been reported to play an important role in HCC, but the effect of sorafenib on microRNAs (miRNAs) and on lung metastasis is not clear. This report employed a high-throughput deep sequencing technique to detect the difference of miRNAs and immunohistochemical technique to detect the difference of protein in implanted primary tumors and in metastatic HCC tumors after treatment with sorafenib. Among the detected miRNAs, we identified rno-miR-122-3p and rmo-miR-122-5p that were downregulated and rno-miR-383-5p and rno-miR-34a-5p that were upregulated and one novel miRNAs is reported as downregulated here for the first time. Immunohistochemical analysis of known miRNAs identified CMYC protein expression as inhibited, MDM2 protein was expressed, and NM23 and GST protein were upregulated. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of novel miRNA found that the targeted genes were concentrated in pathways of metabolism, especially in cytochrome P450. These results indicate that these miRNAs are likely to be involved in the treatment response of lung metastases of HCC to sorafenib. They may be useful as biomarkers to predict the clinical treatment response of sorafenib.

Keywords

Hepatocellular carcinoma (HCC) Lung metastasis Sorafenib MicroRNAs CMYC 

Abbreviations

P53

Protein 53

E-cadherin

E-ca2+-dependent cell adhesion

GST

Glutathione S-transferase

COX-2

Cycloxygenase 2

VEGF

Vascular endothelial growth factor

Bcl-2

B cell lymphoma-2

MDM2

Murine double minute 2

CDK4

Cyclin-dependent kinase 4

EBV

Epstein-Barr virus

Notes

Acknowledgments

This work was supported by National Natural Science Foundation (No. 81272574) and Youth Science Foundation of the Fujian Bureau of Public Health (No. 2011-1-22).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Pathology, School of Basic Medical SciencesFujian Medical UniversityFuzhouChina
  2. 2.Department of Molecular PathologyFujian Provincial Tumor Hospital, The Teaching Hospital of Fujian Medical UniversityFuzhouChina
  3. 3.Fujian Provincial Key Laboratory of Translational Cancer MedicineFuzhouChina

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