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LncRNA n339260 functions in hepatocellular carcinoma progression via regulation of miRNA30e-5p/TP53INP1 expression

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Currently, the molecular mechanism of the interaction between lncRNAs and microRNAs (miRNAs) and the target of miRNAs in tumor vasculogenic mimicry (VM) formation have not been clarified. Our aim is to study the interaction between lncRNA n339260 and miRNA30e-5p in the formation of VM.

Methods

Animal xenografts were established, 104 hepatocellular carcinoma (HCC) patients’ frozen tissues were obtained and HCC cells in vitro were used to observe the role of n339260 in HCC progression.

Results

In vivo experiment showed lncRNA n339260 promoted tumor growth and VM formation. LncRNA n339260 and miRNA30e-5p were found to be associated with VM formation, metastasis and survival time in HCC patients. In vitro experiment showed that LncRNA n339260 could inhibit miRNA30e-5p expression and TP53INP1 was found to be the downstream targets of miRNA30e-5p. Snail, MMP2, MMP9, VE-cadherin, vimentin and N-cadherin overexpression and the downregulation of TP53INP1 and E-cadherin were observed in HCCLM3 and HepG2 cells overexpressing lncRNA n339260 or in cells with decreased expression of miRNA30e-5p.

Conclusion

LncRNA n339260 promotes the development of VM, and lncRNA n339260 may enhance Snail expression by decreasing the expression of miRNA30e-5p, thereby reducing TP53INP1 expression. Therefore, a potential lncRNA n339260- miRNA30e-5p- TP53INP1 regulatory axis was associated with HCC progression.

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Abbreviations

EMT:

Epithelial–mesenchymal transition

HCC:

Hepatocellular carcinoma

IHC:

Immunohistochemical

lncRNA:

Long noncoding RNA

miRNA:

MicroRNA

VM:

Vasculogenic mimicry

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Acknowledgements

This study was partially supported by the following grants: The National Natural Science Foundation of China (No. 81572872).

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Author notes

  1. Tieju Liu, Shihan Liao, and Jing Mo have equally contributed.

Authors and Affiliations

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

    Tieju Liu, Shihan Liao, Jing Mo, Xiaoyu Bai, Yanlei Li, Danfang Zhang, Nan Zhao, Na Che, Xueyi Dong & Xiulan Zhao

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

    Tieju Liu, Jing Mo, Yanlei Li, Danfang Zhang, Nan Zhao, Na Che, Xueyi Dong & Xiulan Zhao

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

    Yanhui Zhang, Runfen Cheng & Yuhong Guo

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  1. Tieju Liu
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Supplementary Information

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535_2022_1901_MOESM1_ESM.tif

Figure S1. (A) The wound healing experiment of lncRNA n339260 upregulated (n339260) and downregulated (n339260-SH) HCC cells. (B) The wound healing experiment of miRNA30e-5p upregulated (30e-5p) and downregulated (inhibitor) HCC cells. (TIF 12459 KB)

535_2022_1901_MOESM2_ESM.tif

Figure S2. (A) The wound healing experiment of TP53INP1 upregulated (TP53INP1) and downregulated (TP53INP1-SH) HCC cells. (B) The wound healing experiment of n339260 and miRNA30e-5p co-transfected HCC cells in rescue experiment. (TIF 3682 KB)

535_2022_1901_MOESM3_ESM.tif

Figure S3. (A) The wound healing experiment of n339260 and miRNA30e-5p co-transfected HCC cells in rescue experiment. (B) The migration experiment, invasion experiment and three-dimensional VM tubules of n339260 and miRNA30e-5p co-transfected HCC cells in rescue experiment. (C) Western blots of TP53INP1, VM marker (MMP2, MMP9 and VE-cadherin) and EMT indexes (snail, E-cadherin and vimentin) expression in lncRNA n339260 and miRNA30e-5p co-transfected HCC cells in rescue experiment. (D) Luciferase reporter gene experiment of miRNA30e-5p and TP53INP1 in 293T cells. Error bars represent the mean ± SD of three independent experiments. (TIF 1117 KB)

535_2022_1901_MOESM4_ESM.tif

Figure S4. (A) The migration experiment, invasion experiment and three-dimensional VM tubules of n339260 and miRNA30e-5p co-transfected HCC cells in rescue experiment. (B) The wound healing experiment of miRNA30e-5p and TP53INP1 co-transfected HCC cells in rescue experiment. (TIF 3548 KB)

535_2022_1901_MOESM5_ESM.tif

Figure S5. (A) The wound healing experiment of miRNA30e-5p and TP53INP1 co-transfected HCC cells in rescue experiment. (B) The migration experiment, invasion experiment and three-dimensional VM tubules of miRNA30e-5p and TP53INP1 co-transfected HCC cells in rescue experiment. (C) Western blots of VM marker (MMP2, MMP9 and VE-cadherin) and EMT indexes (snail, E-cadherin and vimentin) expression of miRNA30e-5p and TP53INP1 co-transfected HCC cells in rescue experiment. Error bars represent the mean ± SD of three independent experiments. (TIF 4104 KB)

535_2022_1901_MOESM6_ESM.tif

Figure S6. (A) The migration experiment, invasion experiment and three-dimensional VM tubules of miRNA30e-5p and TP53INP1 co-transfected HCC cells in rescue experiment. (TIF 5428 KB)

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Liu, T., Liao, S., Mo, J. et al. LncRNA n339260 functions in hepatocellular carcinoma progression via regulation of miRNA30e-5p/TP53INP1 expression. J Gastroenterol 57, 784–797 (2022). https://doi.org/10.1007/s00535-022-01901-8

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  • DOI: https://doi.org/10.1007/s00535-022-01901-8

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