title: Long non-coding RNAs are differentially expressed in hepatocellular carcinoma cell lines with differing metastatic potential.
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.
  
  
  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 (≥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.
authors.affiliation: Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Xuhui, Shanghai, P.R. China E-mail : ren.ning@zs-hospital.sh.cn, liu.binbin@zs-hospital.sh.cn.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Fang
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009362:Neoplasm Metastasis; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger