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Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma

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Tumor Biology

Abstract

Recurrence, invasion, and metastasis are the major reasons of the low 5-year survival of hepatocellular carcinoma. However, the mechanisms of recurrence, invasion, and metastasis are still poll understood. Long noncoding RNAs (LncRNAs, >200 nt) have been demonstrated to play important roles in both tumor suppressive and oncogenic signaling pathways. Here, we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC) tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion, and metastasis process of HCC. Overall, 1170 LncRNAs were identified to differentially expressed between the early and late recurrence samples. These differentially expressed LncRNAs were further characterized by integrating examination of genomic context, co-expression network analysis, and gene ontology (GO) enrichment of their associated protein-coding genes. Furthermore, 15 LncRNAs selected randomly from top 50 differentially expressed LncRNAs were validated by quantitative PCR (qPCR) in cell lines MHCC97H and MHCC97L, which have exactly the same genetic background but with different invasion potentials. Meanwhile, the prognostic potential of three verified LncRNAs at cell line level was further validated in 59 HCC samples. Therefore, our results demonstrated that the aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis and provide fundamental information for further study the LncRNAs involved molecular mechanisms of the invasion and metastasis of HCC.

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Acknowledgments

This work is supported by the Key Clinical Specialty Discipline Construction Program of Fujian, P. R.C.; the Key Project of National Science and Technology of China (Grant no. 2012ZX10002010-001-006 and Grant no. 2012ZX10002016-013), the National Natural Science Foundation of China (Grant no. 31201008), the Key Project of Fujian Province (Grant no. 2013YZ0002-3), the Scientific Foundation of Fuzhou Health Department (Grant no. 2013-S-wq18, and Grant no. 2013-S-wp1), the Mengchao Hepatobiliary Hospital of Fujian Medical University (Grant no. QDZJ-2014-004), the Science and Technology Bureau of Fuzhou City (Grand no. 2014-S-139-1), the Fujian Provincial Health and Family Planning Commission (Grant no. 2014-2-41), and the Research Development Special Fund of Indirectly Affiliated Hospital of Fujian Medical University (Grant no.FZS13004Y).

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Authors and Affiliations

  1. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, China

    Yunzhen Gao, Geng Chen, Yongyi Zeng, Jinhua Zeng, Minjie Lin, Xiaolong Liu & Jingfeng Liu

  2. The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China

    Yunzhen Gao, Geng Chen, Yongyi Zeng, Jinhua Zeng, Minjie Lin, Xiaolong Liu & Jingfeng Liu

  3. Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

    Yongyi Zeng, Jinhua Zeng & Jingfeng Liu

Authors
  1. Yunzhen Gao
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  2. Geng Chen
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  3. Yongyi Zeng
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  4. Jinhua Zeng
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  5. Minjie Lin
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  6. Xiaolong Liu
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  7. Jingfeng Liu
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Corresponding authors

Correspondence to Xiaolong Liu or Jingfeng Liu.

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Fig. 1

Hierarchical clustering of the differentially expressed LncRNAs and mRNAs in the primary HCC tissues from patients group T1, T2 and NT; T1 represents patients who had recurrence within one year after surgical resection and with outside liver metastasis; T2 represents patients who and recurrence after 2 years of surgical resection and without outside liver metastasis; NT represents normal liver tissues. (A) Differentially expressed LncRNAs between comparison of T1 and NT; (B) differentially expressed mRNAs between comparison of T2 and NT. Red color indicates the up-regulation and green color indicates the down regulation. (PDF 216 kb)

Fig. 2

The distribution of differentially expressed LncRNAs and mRNAs on each chromosome in the comparison between T1 and NT (A) and in the comparison between T2 and NT (B); T1 represents patients who had recurrence within one year after surgical resection and with outside liver metastasis; T2 represents patients who and recurrence after 2 years of surgical resection and without outside liver metastasis; NT represents normal liver tissues. The percentage of LncRNAs and mRNAs distributed on each chromosome, was calculated by the numbers of LncRNAs and mRNAs on each chromosome dividing the total numbers of differentially expressed LncRNAs and mRNAs; ch represents chromosome. (PDF 263 kb)

Fig. 3

The distribution of up- and down-regulated LncRNAs (A) and mRNAs (B) on each chromosome in the comparison between T1 and NT and the distribution of up- and down-regulated LncRNA (C) and mRNA (D) in the comparison between T2 and NT; T1 represents patients who had recurrence within one year after surgical resection and with outside liver metastasis; T2 represents patients who and recurrence after 2 years of surgical resection and without outside liver metastasis; NT represents normal liver tissues. (PDF 82 kb)

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Gao, Y., Chen, G., Zeng, Y. et al. Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma. Tumor Biol. 36, 7409–7422 (2015). https://doi.org/10.1007/s13277-015-3408-0

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