Hormones and Cancer

, Volume 10, Issue 4–6, pp 177–189 | Cite as

Downregulation of miR-196-5p Induced by Hypoxia Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma

  • Hao Zheng
  • Feng-rui Bi
  • Yuan Yang
  • Yong-gang Hong
  • Jun-sheng Ni
  • Long Ma
  • Ming-hua Liu
  • Li-qiang Hao
  • Wei-ping ZhouEmail author
  • Li-hua SongEmail author
  • Hong-Li YanEmail author
Original Paper


In hepatocellular carcinoma (HCC), the hypoxic tumor microenvironment can drive enhance tumor malignancy and recurrence. The microRNA (miRNA) miR-196-5p has been shown to modulate the progression of several cancer types, but its roles in HCC remain uncertain. In the present report we observed significant miR-196-5p downregulation in HCC tissues and cells, and we found that the expression of this miRNA significantly impaired the proliferation and metastatic potential of HCC in vitro and in vivo. We identified high-mobility group AT-hook 2 (HMGA2) as a miR-196-5p target gene that was associated with the ability of miR-196-5p to modulate the progression of HCC. Expression of miR-196-5p and HMGA2 were correlated with the clinical characteristics and poor outcomes in patients with HCC. Finally, we found that hypoxic conditions were linked with reduced miR-196-5p expression in the context of HCC. Together these results highlight the role for miR-196-5p as an inhibitor of the proliferation and metastasis of HCC via the targeting of HMGA2, with this novel hypoxia/miR-196-5p/HMGA2 pathway serving as a potential target for future therapeutic intervention.


Hepatocellular carcinoma miR-196-5p HMGA2 Biomarker Hypoxia 


Funding Information

The study was funded by the National Natural Science Foundation of China (NSFC81672350, 81872225); the National Key Basic Research Program of China (grant no. 2014CB542102); The Shanghai Health and Family Planning Commission Foundation (grant no. 20164Y0189); The National Human Genetic Resources Sharing Service Platform (grant no. 2005DKA21300); The Science Fund for Creative Research Groups, NSFC, China (grant no. 81521091); the NewtritionTM Asia Research Grant by BASF and National Natural Science Foundation of China (Grant No. 81672350, 81872225); and The State Key Infection Disease Project of China (grant no. 2017ZX10203208).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hao Zheng
    • 1
    • 2
    • 3
    • 4
  • Feng-rui Bi
    • 1
  • Yuan Yang
    • 2
    • 3
    • 4
  • Yong-gang Hong
    • 5
  • Jun-sheng Ni
    • 2
    • 3
    • 4
  • Long Ma
    • 1
  • Ming-hua Liu
    • 1
  • Li-qiang Hao
    • 5
  • Wei-ping Zhou
    • 2
    • 3
    • 4
    Email author
  • Li-hua Song
    • 6
    Email author
  • Hong-Li Yan
    • 1
    Email author
  1. 1.Department of Reproductive Heredity Center, Changhai HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.Key Laboratory of Signalling Regulation and Targeting Therapy of Liver Cancer (SMMU)Ministry of EducationShanghaiPeople’s Republic of China
  4. 4.Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH)ShanghaiPeople’s Republic of China
  5. 5.Department of Colorectal Surgery, Changhai HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  6. 6.School of Agriculture and BiologyShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China

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