Tumor Biology

, Volume 37, Issue 8, pp 10965–10979 | Cite as

Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p

  • Yong Wang
  • Baocun Sun
  • Huizhi Sun
  • Xiulan Zhao
  • Xudong Wang
  • Nan Zhao
  • Yanhui Zhang
  • Yanlei Li
  • Qiang Gu
  • Fang Liu
  • Bing Shao
  • Jindan An
Original Article

Abstract

MicroRNAs (miRNAs) play vital roles in cell proliferation, differentiation and apoptosis in hepatocellular carcinoma (HCC). miR-26b has been confirmed as an important regulator in carcinogenesis and other pathological processes. miR-26b-5p is one member of the mature miR-26 family, and its functional role in proliferation, angiogenesis and apoptosis in HCC remains unknown. Here, we demonstrate that miR-26b-5p expression was significantly decreased in HCC tissues and HCC cell lines compared with normal liver tissues and liver cells by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between miR-26b-5p and the clinical characteristics of HCC patients were further analysed, and miR-26b-5p was positively correlated with the differentiation of HCC cells. Computational searches were further used to identify the downstream targets and signalling pathways of miR-26b-5p in HCC cells. Cell viability, proliferation and tube formation abilities were assessed by scrape, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and three-dimensional culture assays to confirm that miR-26b-5p inhibited HCC cell growth and impaired the tube formation ability of the HCC cells. Both in vitro and in vivo studies showed that miR-26b-5p could suppress vascular mimicry (VM) and angiogenesis by down-regulating the expression of VE-cadherin, Snail and MMP2 and could inhibit the apoptosis of HCC cells. Using mouse models, we revealed that tumours derived from miR-26b-5p-expressing HCC cells displayed a significant decrease in microvessel density compared with those derived from control cells. Therefore, our data provide further insight into the role of miR-26b-5p as a negative regulator of proliferation, angiogenesis, and apoptosis in HCC.

Keywords

miR-26b-5p Angiogenesis Apoptosis Hepatocellular carcinoma 

Notes

Acknowledgments

This study was funded by the Key project of the National Natural Science Foundation of China (no. 81230050), the National Natural Science Foundation of China (no. 81172046, no. 81173091 and no. 81301813), the Key project of the Tianjin Natural Science Foundation (no. 12JCZDJC23600) and the project of the Tianjin Natural Science Foundation (No. 14JCYBJC27700).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

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ESM 1 (DOC 33 kb)
13277_2016_4964_MOESM2_ESM.doc (12 kb)
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13277_2016_4964_MOESM3_ESM.doc (16 kb)
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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yong Wang
    • 1
  • Baocun Sun
    • 1
    • 2
    • 3
    • 5
  • Huizhi Sun
    • 1
  • Xiulan Zhao
    • 1
    • 3
  • Xudong Wang
    • 2
  • Nan Zhao
    • 1
  • Yanhui Zhang
    • 2
  • Yanlei Li
    • 1
  • Qiang Gu
    • 1
    • 3
  • Fang Liu
    • 1
    • 3
  • Bing Shao
    • 1
  • Jindan An
    • 4
  1. 1.Department of PathologyTianjin Medical UniversityTianjinChina
  2. 2.Department of Pathology, Tianjin Cancer HospitalTianjin Medical UniversityTianjinChina
  3. 3.Department of Pathology, Tianjin General HospitalTianjin Medical UniversityTianjinChina
  4. 4.Department of PathologyMudanjiang Medical UniversityHeilongjiangChina
  5. 5.Department of Pathology and Cancer Hospital and General Hospital of TianjinMedical UniversityTianjinChina

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