Research Paper Volume 14, Issue 3 pp 1473—1491
Identification of an EMT-related lncRNA signature and LINC01116 as an immune-related oncogene in hepatocellular carcinoma
- 1 Hepatic Surgery Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- 2 Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, China
- 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Received: August 16, 2021 Accepted: January 17, 2022 Published: February 11, 2022
https://doi.org/10.18632/aging.203888How to Cite
Copyright: © 2022 Tao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Epithelial–mesenchymal transition (EMT) plays a critical role in the recurrence and metastasis of hepatocellular carcinoma (HCC). Some long noncoding (lnc)RNAs are involved in this process through the regulation of EMT-related transcription factors.
Methods: In this study, we established a novel EMT-related lncRNA signature in HCC and identified hub lncRNAs that can serve as potential therapeutic targets. Differentially expressed lncRNAs were identified by screening HCC patient data from The Cancer Genome Atlas, and a correlation analysis was performed to identify those associated with EMT. The EMT-related lncRNA signature was established by univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. After verifying the prognostic accuracy of the signature, its relationships to immune cell infiltration and immune checkpoint targets were explored. LINC01116 was identified as a hub lncRNA and its role in HCC was investigated in vitro and in vivo.
Results: A 5-lncRNA signature was developed for HCC and its prognostic accuracy was assessed by survival, time-dependent receiver operating characteristic curve, clinical correlation, and Cox regression analyses. The correlation analysis showed that the lncRNA signature was closely related to immune cell infiltration and 10 immune checkpoint targets and also predicted the prognosis of HCC patients with high accuracy. In vitro and in vivo experiments revealed that LINC01116 stimulated cell proliferation, cell cycle progression, and tumor metastasis. We also found that LINC01116 was closely related to immune regulation.
Conclusions: These results demonstrate that LINC01116 is an immune-related oncogene that is associated with both EMT and immune regulation in HCC. Moreover, the EMT-related lncRNA signature that includes LINC01116 can guide risk stratification and clinical decision-making in HCC management.