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Long Non-coding RNA TTN Antisense RNA 1 Facilitates Hepatocellular Carcinoma Progression Via Regulating MiR-139-5p/SPOCK1 Axis

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Journal Bioengineered
Date 2021 Feb 1
PMID 33517826
Citations 18
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Abstract

Reportedly, long non-coding RNAs (lncRNAs) are implicated in hepatocellular carcinoma (HCC) progression, yet little is known concerning the biological functions of TTN antisense RNA 1 (TTN-AS1) in HCC. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting TTN-AS1, SPOCK1 mRNA, and miR-139-5p expressions in HCC cells and tissues. After TTN-AS1 was overexpressed or knocked down in HCC cells, CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were carried out for examining cell multiplication. Transwell assays were conducted for evaluating HCC cell migration and invasion. Dual-luciferase reporter assay was employed for verifying the binding relationships between miR-139-5p and TTN-AS1, and between SPOCK1 3'UTR and miR-139-5p. Western blot was employed to measure SPOCK1, E-cadherin, N-cadherin, and Vimentin protein expressions. We demonstrated that, TTN-AS1 and SPOCK1 expression levels were remarkably enhanced in HCC cells and tissues, whereas miR-139-5p expression was observably reduced. Functional experiments suggested that TTN-AS1 knockdown markedly repressed HCC cell multiplication, migration, epithelial-mesenchymal transition (EMT), and invasion. In addition, TTN-AS1 interacted with miR-139-5p and decreased its expression. Moreover, SPOCK1 was a miR-139-5p target, and miR-139-5p inhibitors were able to reverse TTN-AS1 knockdown-induced inhibitory effect on SPOCK1 expression. SPOCK1 overexpression plasmid could counteract TTN-AS1 knockdown-induced inhibiting impact on HCC cell multiplication, migration, invasion, and EMT. In conclusion, TTN-AS1 expression level is remarkably enhanced in HCC, and TTN-AS1 can promote the multiplication, migration, invasion, and EMT of HCC cells via regulating miR-139-5p/SPOCK1 axis.

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References
1.
Dey B, Mueller A, Dutta A . Long non-coding RNAs as emerging regulators of differentiation, development, and disease. Transcription. 2014; 5(4):e944014. PMC: 4581346. DOI: 10.4161/21541272.2014.944014. View

2.
Zhou Y, Huang Y, Dai T, Hua Z, Xu J, Lin Y . LncRNA TTN-AS1 intensifies sorafenib resistance in hepatocellular carcinoma by sponging miR-16-5p and upregulation of cyclin E1. Biomed Pharmacother. 2020; 133:111030. DOI: 10.1016/j.biopha.2020.111030. View

3.
Qiu G, Lin Y, Zhang H, Wu D . miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2. Biochem Biophys Res Commun. 2015; 463(3):315-21. DOI: 10.1016/j.bbrc.2015.05.062. View

4.
Liu S, Qiu J, He G, Liang Y, Wang L, Liu C . LncRNA MALAT1 acts as a miR-125a-3p sponge to regulate FOXM1 expression and promote hepatocellular carcinoma progression. J Cancer. 2019; 10(26):6649-6659. PMC: 6856878. DOI: 10.7150/jca.29213. View

5.
Zhang J, Zhi X, Shi S, Tao R, Chen P, Sun S . SPOCK1 is up-regulated and promotes tumor growth via the PI3K/AKT signaling pathway in colorectal cancer. Biochem Biophys Res Commun. 2016; 482(4):870-876. DOI: 10.1016/j.bbrc.2016.11.126. View