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LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity

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Abstract

Purpose

Emerging evidence indicates that dysfunction of long non-coding RNAs (lncRNAs) plays an essential role in the initiation and progression of hepatocellular carcinoma (HCC). In this study we investigated the potential roles and molecular mechanisms involving LINC01419 in HCC.

Methods

The expression of LINC01419 in 40 pairs of HCC/normal tissues and 6 HCC cell lines was detected by qRT-PCR. MTS, EdU, colony formation, scratch wound-healing and transwell assays were performed to assess the role of LINC01419 in HCC cell (SMMC7721 and SK-Hep1) proliferation, migration and invasion in vitro. Artificial modulation of LINC01419 (up- and downregulation) was performed to explore the role of LINC01419 in tumor growth and metastasis in vivo. Interaction of LINC01419 with NDRG1 was assessed using qRT-PCR, RNA sequencing, Western blotting and immunohistochemistry. Physical interaction of LINC01419 with the NDRG1 promoter was assessed using a dual-luciferase reporter assay.

Results

We observed LINC01419 overexpression in primary HCC tissues and HCC cell lines and that this overexpression positively correlated with large tumor size, increased vascular invasion and advanced TNM stage in 40 HCC patients. Exogenous LINC01419 expression significantly promoted HCC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, we found that LINC01419 expression knockdown elicited opposite effects. Mechanistic investigations revealed that LINC01419 exerted its biological effects by regulating NDRG1. A dual-luciferase reporter assay revealed that LINC01419 interacts with a specific region within the NDRG1 promoter, resulting in its activation.

Conclusions

From our data we conclude that LINC01419 acts clinically, functionally and mechanistically oncogenic in HCC. LINC01419 may, therefore, serve as a promising prognostic indicator and therapeutic target for HCC.

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Funding

This study was supported by a National Science and Technology Major Project of the Ministry of Science and Technology of China [grant number 2018ZX10732202], and a Postgraduate scientific research innovation project of Chongqing, China [grant number CYB18164].

Author information

Author notes

  1. Hao Dang, Ling Chen and Ping Tang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Yi Xue Yuan Road, Chongqing, 400016, China

    Hao Dang, Ling Chen, Xuefei Cai, Wenlu Zhang, Ailong Huang & Hua Tang

  2. Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan mental health center), Mianyang, Sichuan, China

    Hao Dang & Renfei Zhang

  3. Department of Head and Neck Surgery, The Third Hospital of Mianyang (Sichuan mental health center), Mianyang, Sichuan, China

    Ping Tang

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  1. Hao Dang
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Correspondence to Hua Tang.

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Ethics approval and consent to participate

This study was approved by the ethics committee of the Third Hospital of Mianyang, and informed consent was obtained from each patient. Animal studies were approved by the Ethics Committee of Animal Experiments of Chongqing Medical University.

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Fig. S1

Transcript location of LINC01419. (a) The LINC01419-coding sequence with the length of 1521 bp (NCBI Accession: NR_122034.1), consisting of exons 1 and 2, is located on chromosome 8 (q21.13). The image is shown by HUGO Gene Nomenclature Committee (HGNC, https://www.genenames.org/). (b) The schematic model of LINC01419 sequence structure. The image is shown by LNCipedia (https://www.lncipedia.org/). (PNG 262 kb)

High resolution image (TIF 1112 kb)

Fig. S2

LINC01419 is mainly localized in the cell cytoplasm. The image is shown by lncLocator (http://www.csbio.sjtu.edu.cn/bioinf/lncLocator/). (PNG 492 kb)

High resolution image (TIF 96 kb)

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Dang, H., Chen, L., Tang, P. et al. LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity. Cell Oncol. 43, 931–947 (2020). https://doi.org/10.1007/s13402-020-00540-6

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