LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity
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ORIGINAL PAPER
LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity Hao Dang 1,2
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& Ling Chen & Ping Tang & Xuefei Cai & Wenlu Zhang & Renfei Zhang & Ailong Huang & Hua Tang
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Accepted: 5 June 2020 # International Society for Cellular Oncology 2020
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 (upand 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. Keywords Hepatocellular carcinoma . LINC01419 . NDRG1 . Proliferation . Metastasis
Hao Dang, Ling Chen and Ping Tang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00540-6) contains supplementary material, which is available to authorized users. * Hua Tang [email protected]
Renfei Zhang [email protected]
Hao Dang [email protected] Ling Chen [email protected]
Ailong Huang [email protected] 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
Xuefei Cai [email protected]
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