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

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Tumor Biology

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.

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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).

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    Authors and Affiliations

    1. Department of Pathology, Tianjin Medical University, Tianjin, 300070, China

      Yong Wang, Baocun Sun, Huizhi Sun, Xiulan Zhao, Nan Zhao, Yanlei Li, Qiang Gu, Fang Liu & Bing Shao

    2. Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China

      Baocun Sun, Xudong Wang & Yanhui Zhang

    3. Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, 300052, China

      Baocun Sun, Xiulan Zhao, Qiang Gu & Fang Liu

    4. Department of Pathology, Mudanjiang Medical University, Heilongjiang, 157011, China

      Jindan An

    5. Department of Pathology and Cancer Hospital and General Hospital of Tianjin, Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, China

      Baocun Sun

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    1. Yong Wang
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    Yong Wang and Baocun Sun contributed equally to this work.

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    Wang, Y., Sun, B., Sun, H. et al. Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p. Tumor Biol. 37, 10965–10979 (2016). https://doi.org/10.1007/s13277-016-4964-7

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