Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2021; 27(20): 2586-2602
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2586
Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma
Guang-Lin Lei, Yan Niu, Si-Jie Cheng, Yuan-Yuan Li, Zhi-Fang Bai, Ling-Xiang Yu, Zhi-Xian Hong, Hu Liu, Hong-Hong Liu, Jin Yan, Yuan Gao, Shao-Geng Zhang, Zhu Chen, Rui-Sheng Li, Peng-Hui Yang
Guang-Lin Lei, Si-Jie Cheng, Yuan-Yuan Li, Zhi-Fang Bai, Ling-Xiang Yu, Zhi-Xian Hong, Hu Liu, Hong-Hong Liu, Jin Yan, Yuan Gao, Shao-Geng Zhang, Zhu Chen, Rui-Sheng Li, Peng-Hui Yang, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Yan Niu, Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia Autonomous Region, China
Author contributions: Lei GL and Niu Y contributed equally to this work; Li RS and Yang PH are both corresponding authors; Lei GL and Niu Y performed the experiments and wrote the manuscript; Cheng SJ, Li YY, Bai ZF, Yu LX, Hong ZX and Liu H collected the data; Liu HH, Yan J, Gao Y, Zhang SG, Chen Z, Li RS and Yang PH analyzed the data; all authors approved the final version of the article.
Institutional review board statement: This study was approved by the Ethics Committee of the Fifth Medical Center of Chinese PLA General Hospital, and carried out according to the Declaration of Helsinki.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Fifth Medical Center of Chinese PLA General Hospital.
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Peng-Hui Yang, MD, Professor, Fifth Medical Center of Chinese PLA General Hospital, No. 100 Xisihuan Zhong Road, Fengtai District, Beijing 100039, China. ypenghuiamms@hotmail.com
Received: November 18, 2020
Peer-review started: November 18, 2020
First decision: January 23, 2021
Revised: February 10, 2021
Accepted: April 2, 2021
Article in press: April 2, 2021
Published online: May 28, 2021
Processing time: 182 Days and 23.3 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is a malignancy found globally. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play critical roles in HCC. However, the function of lncRNA in HCC remains poorly understood.

AIM

To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.

METHODS

We measured the expression of lncRNA W42 in HCC tissues and cells (Huh7 and SMMC-7721) by quantitative reverse transcriptase polymerase chain reaction. Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression. HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42. Cell functions were detected by cell counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays. The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays. An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo. The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.

RESULTS

In this study, we identified a novel lncRNA (lncRNA W42), and investigated its biological functions and clinical significance in HCC. LncRNA W42 expression was upregulated in HCC tissues and cells. Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC, and inhibited cell apoptosis. LncRNA W42 directly bound to DBN1 and activated the downstream pathway. LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo. The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.

CONCLUSION

In vitro and in vivo results suggested that the novel lncRNA W42, which is upregulated in HCC, may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

Keywords: Hepatocellular carcinoma; Long noncoding RNA; Long noncoding RNA W42; Tumor; DBN1; Cancer

Core Tip: The results of this study demonstrated, for the first time, that long noncoding RNA (lncRNA) W42 expression was significantly higher in hepatocellular carcinoma (HCC) tissues than in normal tissues and that dysregulation of lncRNA W42 was positively correlated with tumor number, liver cirrhosis and tumor recurrence in patients with HCC. Moreover, increased lncRNA W42 expression was associated with a poor prognosis in patients with HCC. These findings suggest that lncRNA W42 is an important marker for indicting prognosis and may have potential as a diagnostic and therapeutic target for HCC.