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

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellularcarcinoma (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: Inthis 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 LncRNAArray 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 withpotential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representativemRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differingmetastasis potential by qRT-PCR.
Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAsthat were differentially expressed (≥1.5 fold-change) between the two HCC cell lines. The most upregulatedlncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated oneswere lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulatedmRNAs 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 lungmetastatic 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 expressedin no lymphatic metastatic potential HCC cell lines.
Conclusions: We provide the first detailed description oflncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large numberof lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs mayprovide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.