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Downregulation of LncRNA GAS5 promotes liver cancer proliferation and drug resistance by decreasing PTEN expression

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Abstract

Accumulating evidence has shown that the long noncoding RNAs (lncRNAs) play a crucial role in the regulation of hepatocellular carcinoma (HCC) progression and drug resistance. In this study, we aimed to investigate the biological function roles of lncRNAs growth arrest-specific 5 (GAS5) and its underlying molecular mechanism in the development of HCC. qRT-PCR was used to detect GAS5, miR-21, and PTEN levels. MTT, cell counting assays, and xenograft mouse model were applied to measure cell proliferation rate in vitro and in vivo. The luciferase reporter assay and RNA immune-precipitation assay were introduced to evaluate the relationship between GAS5 and miR-21. We found that GAS5 was downregulated in HCC cell lines and tumor tissues. Knockdown of GAS5 enhanced HCC cell proliferation in vitro and in vivo and increased HCC cell resistance to doxorubicin. GAS5 acted as a sponge for miR-21 silencing and consequently led to the elevation of PTEN expression. Our data demonstrated that GAS5 functioned as a tumor suppressor role in HCC through regulation of miR-21-PTEN singling pathways, suggesting a potential application of GAS5 in HCC therapy.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China

    Congren Wang, Shaoying Ke, Mingzhu Li, Conglin Lin, Xiaoyu Liu & Qunxiong Pan

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  1. Congren Wang
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  2. Shaoying Ke
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  3. Mingzhu Li
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  4. Conglin Lin
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  5. Xiaoyu Liu
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  6. Qunxiong Pan
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Correspondence to Qunxiong Pan.

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Communicated by Stefan Hohmann.

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Wang, C., Ke, S., Li, M. et al. Downregulation of LncRNA GAS5 promotes liver cancer proliferation and drug resistance by decreasing PTEN expression. Mol Genet Genomics 295, 251–260 (2020). https://doi.org/10.1007/s00438-019-01620-5

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  • DOI: https://doi.org/10.1007/s00438-019-01620-5

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