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Long non-coding RNA NEAT1 promotes colorectal cancer progression by regulating miR-205-5p/VEGFA axis

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Abstract

Long non-coding RNAs (lncRNAs) play key roles in tumorigenesis. It has been reported that the lncRNA nuclear-enriched abundant transcript 1 (NEAT1) may act as an oncogenic regulator in several cancers. However, the biological mechanism of action of NEAT1, particularly the miRNA sponge role in colorectal cancer (CRC), has not been fully elucidated. In our study, the expression of NEAT1, miR-205-5p, and vascular endothelial growth factor A (VEGFA) in CRC cell lines were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were examined by wound healing and transwell assays, respectively. RNA-binding protein immunoprecipitation (RIP), and dual-luciferase and RNA pull-down assays were conducted to determine the correlation between miR-205-5p and NEAT1 or VEGFA. VEGFA, matrix metalloproteinase (MMP)2, and MMP9 protein and mRNA expression were measured by western blotting and RT-qPCR analysis, respectively. Our results demonstrated high expression of NEAT1 and VEGFA and low expression of miR-205-5p in CRC cell lines. The RIP and dual-luciferase assays confirmed miR-205-5p as a target of NEAT1. In addition, VEGFA was identified as a direct target of miR-205-5p. Inhibition of NEAT1 or overexpression of miR-205-5p was able to repress VEGFA expression. Moreover, downregulation of NEAT1 and VEGFA inhibited cell proliferation, migration, and invasion. NEAT1 overexpression facilitated tumor growth by modulating miR-205-5p. Taken together, lncRNA NEAT1 was found to be upregulated in CRC cell lines, promoting CRC cell proliferation, migration, and invasion through regulating the miR-205-5p/VEGFA signaling pathway. These findings suggest that NEAT1 may be a promising biomarker in CRC diagnosis and treatment.

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Acknowledgements

The present study was supported by Jiangsu University Medical Clinical Science and Technology Development Fund Project (Grant JLY20140133).

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Author notes

  1. Huijie Liu and Aiyi Li have equally contributed to this work.

Authors and Affiliations

  1. Department of Breast Oncology, Xiang Yang Central Hospital, The Affiliated Hospital of Hubei College of Arts and Sciences, 136 Jingzhou Street, Xiangyang, 441021, Hubei, China

    Huijie Liu & Hua Xu

  2. Disinfection Supply Center, The Second People’s Hospital of Lianyungang, Lianyungang, 222023, China

    Aiyi Li

  3. Department of Pathology, The Second People’s Hospital of Lianyungang, Lianyungang, 222023, China

    Zhichao Sun

  4. Department of Tumor-Chemotherapy, The Second People’s Hospital of Lianyungang, 161 Xingfu Road, Haizhou, Lianyungang, 222023, Jiangsu, China

    Jingyu Zhang

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  1. Huijie Liu
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  2. Aiyi Li
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  4. Jingyu Zhang
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  5. Hua Xu
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Correspondence to Jingyu Zhang or Hua Xu.

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The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Ethics Committee of The Second People’s Hospital of Lianyungang (2014030), and written informed consent was obtained from all the patients. All the procedures were performed in accordance with the principles outlined in the Declaration of Helsinki and relevant policies in China.

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Liu, H., Li, A., Sun, Z. et al. Long non-coding RNA NEAT1 promotes colorectal cancer progression by regulating miR-205-5p/VEGFA axis. Human Cell 33, 386–396 (2020). https://doi.org/10.1007/s13577-019-00301-0

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  • DOI: https://doi.org/10.1007/s13577-019-00301-0

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