Tumor Biology

, Volume 37, Issue 2, pp 2691–2702 | Cite as

Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21

  • Litian Hu
  • Hua Ye
  • Guangming Huang
  • Fei Luo
  • Yawei Liu
  • Yi Liu
  • Xiaojun Yang
  • Jian Shen
  • Qizhan Liu
  • Jianping Zhang
Original Article


Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers. Although lncRNA GAS5 (growth arrest-specific transcript 5) has been characterized as a tumor suppressor in some kinds of cancer, its role and function in hepatocellular carcinoma (HCC) remain unknown. The present report demonstrates that there are lower levels of GAS5, PDCD4, and PTEN and higher levels of microRNA-21 (miR-21) in HCC tissues than in adjacent normal tissues. Moreover, the levels of GAS5 and miR-21 were correlated with the clinicopathological characteristics of HCC. HCC patients with higher levels of GAS5 or with the lower levels of miR-21 have longer survival times. There are lower levels of GAS5 and higher levels of miR-21 in HCC cell lines (Be7402, SMMC-7721, and HCCLM3) than in normal liver L-02 cells, and the levels correlate with the aggression of the HCC cell lines. Knockdown of GAS5 upregulates miR-21 levels in Bel-7402 cells (weakly aggressive); in contrast, there are opposite changes in HCCLM3 cells (highly aggressive). Moreover, GAS5 that upregulated or downregulated the expression of PDCD4 and PTEN was reversed by inhibiting or overexpressing miR-21 level in Bel-7402 and HCCLM3 cells. Then, overexpression of GAS5 suppresses the migration and invasion of HCC cells and high expression of miR-21 largely eliminates GAS5-mediated suppression of HCC cell migration and invasion. Thus, GAS5 acts as a tumor suppressor in HCCs through negative regulation of miR-21 and its targets and proteins about migration and invasion in cancer cells, which may be a target for treating HCC.


Hepatocellular carcinoma lncRNA GAS5 miR-21 Migration and invasion 



The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA) for editing. This work was supported by the Natural Science Foundations of China (81272713, 81273114, and 81100253), Natural Science Foundations of Jiangsu Province (BK20131437), and by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (2010).

Conflicts of interest


Supplementary material

13277_2015_4111_MOESM1_ESM.pdf (239 kb)
ESM 1 (PDF 239 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Litian Hu
    • 1
  • Hua Ye
    • 2
  • Guangming Huang
    • 3
  • Fei Luo
    • 4
    • 5
  • Yawei Liu
    • 1
  • Yi Liu
    • 4
    • 5
  • Xiaojun Yang
    • 1
  • Jian Shen
    • 1
  • Qizhan Liu
    • 4
    • 5
  • Jianping Zhang
    • 1
  1. 1.Department of General Surgery, The Second Affiliated HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.School of MedicineYangzhou UniversityYangzhouPeople’s Republic of China
  3. 3.Institute for Digestive Endoscopy and Medical Center for Digestive Disease, The Second Affiliated HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.Institute of Toxicology, School of Public HealthNanjing Medical UniversityNanjingPeople’s Republic of China
  5. 5.The Key Laboratory of Modern ToxicologyMinistry of Education, School of Public Health, Nanjing Medical UniversityNanjingPeople’s Republic of China

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