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Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential

  • Fang, Ting-Ting (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Sun, Xiao-Jing (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Chen, Jie (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Zhao, Yan (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Sun, Rui-Xia (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Ren, Ning (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital) ;
  • Liu, Bin-Bin (Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital)
  • Published : 2015.01.06

Abstract

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

Keywords

Hepatocellular carcinoma;organ-specific metastasis;long non-coding RNA;RP5-1014O16.1;expression

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