Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2024; 30(8): 919-942
Published online Feb 28, 2024. doi: 10.3748/wjg.v30.i8.919
Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma
Ren-Yong Wang, Jia-Ling Yang, Ning Xu, Jia Xu, Shao-Hua Yang, Dao-Ming Liang, Jin-Ze Li, Hong Zhu
Ren-Yong Wang, Ning Xu, Shao-Hua Yang, Dao-Ming Liang, Hong Zhu, Second Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan Province, China
Jia-Ling Yang, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
Jia Xu, Wuhan Blood Center, Wuhan 430030, Hubei Province, China
Jin-Ze Li, Department of Gastrointestinal Surgery, The Third People's Hospital of Hubei Province, Wuhan 430071, Hubei Province, China
Co-first authors: Ren-Yong Wang and Jia-Ling Yang.
Co-corresponding authors: Jin-Ze Li and Hong Zhu.
Author contributions: Wang RY, Yang JL, Xu N, Liang DM, Li JZ and Zhu H designed research; Wang RY, Yang JL, Xu J and Yang SH performed research; Wang RY and Yang JL contributed new reagents or analytic tools; Wang RY, Yang JL, Li JZ and Zhu H analyzed data; Wang RY, Yang JL, Li JZ and Zhu H wrote the paper. All authors contributed to the study design, interpretation of the investigations, data analysis, and manuscript review. Wang RY and Yang JL are listed as co-first authors because they made equal and significant contributions throughout the research process, being jointly responsible for key aspects such as experimental design and data analysis. On the other hand, Li JZ and Zhu H are designated as co-corresponding authors due to their crucial roles in the research design and experimental processes, overseeing the entire study’s planning and supervision, as well as being responsible for interpreting the data and publishing the results. In summary, the authorship order reflects their actual contributions and roles in the research.
Supported by National Natural Science Foundation of China, No. 81460132; and Yunnan Pacific Department of Science, Technology-Kunming Medical University Applied Basic Research Joint Special Fund Project, No. 2018FE001 (-224).
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Second Affiliated Hospital of Kunming Medical University (2021128).
Institutional animal care and use committee statement: All animal experimental procedures and steps were strictly reviewed by the Ethics Review Committee for Animal Experiments at Kunming Medical University (Approval Number: kmmu20211188).
Conflict-of-interest statement: There are no conflicts of interest to disclose in this article.
Data sharing statement: The data supporting the conclusions of this study can be obtained from the corresponding author under reasonable requirements. Normalized RNA-seq data of 50 normal and 374 HCC samples were obtained from TCGA (https://www.cancer.gov/ccg/research/genome-sequencing/tcga).
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Zhu, PhD, Professor, Second Affiliated Hospital of Kunming Medical University, No. 374 Dian-Mian Avenue, Wuhua District, Kunming 650106, Yunnan Province, China. zhuhong@kmmu.edu.cn
Received: November 2, 2023
Peer-review started: November 2, 2023
First decision: December 6, 2023
Revised: December 24, 2023
Accepted: January 27, 2024
Article in press: January 27, 2024
Published online: February 28, 2024
Processing time: 116 Days and 0.5 Hours
ARTICLE HIGHLIGHTS
Research background

Published studies have demonstrated the impact of disturbances in lipid metabolism on the progression of hepatocellular carcinoma (HCC), which is a prevalent form of cancer.

Research motivation

Long noncoding RNAs (lncRNAs) modulate fatty acid metabolism and influence HCC development through pathways involving transcription factors and lipid-related processes. Understanding the role of metabolic reprogramming and lncRNAs in HCC may lead to novel diagnostic markers and therapeutic targets.

Research objectives

This study aims to investigate a novel lncRNA, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

Research methods

The study identified three lipid metabolism-related lncRNAs (LMR-lncRNAs), negative regulator of antiviral response (NRAV), RNA transmembrane and coiled-coil domain family 1 antisense RNA 1 (TMCC1-AS1), and RP11-817I4.1, as predictive markers for HCC and used them to construct risk models. Knockdown of RP11-817I4.1 decreased proliferation, migration, and invasion in HCC cells. RP11-817I4.1 was found to increase lipid levels in HCC cells through the miR-3120-3p/ATP citrate lyase (ACLY) axis, highlighting its role in lipid metabolism and HCC progression.

Research results

The study identified three LMR-lncRNAs, NRAV, TMCC1-AS1, and RP11-817I4.1, as predictive markers for HCC patients and utilized them in constructing risk models. Knockdown of RP11-817I4.1 resulted in reduced proliferation, migration, and invasion of HCC cells. Moreover, RP11-817I4.1 was found to significantly increase lipid levels in HCC cells through the miR-3120-3p/ACLY axis. These findings provide valuable insights into the molecular processes of HCC, uncover novel prognostic indicators and molecular targets, and highlight the therapeutic potential of RP11-817I4.1 in the context of HCC treatment.

Research conclusions

In this study, the functions of LMR-lncRNAs were investigated for their role in assessing and predicting the prognosis of HCC patients, leading to the establishment of an accurate and reliable lipid metabolism-related risk score model for prediction. Of particular interest was the novel LMR-lncRNA, RP11-817I4.1, which was found to regulate HCC lipid metabolism and tumor progression, showing potential as a therapeutic target. The findings hold significant promise for understanding the molecular processes in HCC, identifying novel prognostic indicators, and uncovering molecular targets for potential therapeutic interventions.

Research perspectives

Lipid metabolism-related lncRNA RP11-817I4.1 may be a potential therapeutic target, and the development of small molecule drugs targeting RP11-817I4.1 may help improve the prognosis of HCC patients.