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脂质代谢相关长非编码 RNA RP11-817I4.1 促进肝癌中脂肪酸的合成和肿瘤进展。

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma.

机构信息

Second Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan Province, China.

School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2024 Feb 28;30(8):919-942. doi: 10.3748/wjg.v30.i8.919.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common types of tumors. The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.

AIM

To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs (LMR-lncRNAs) and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.

METHODS

Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs. Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs. Nile red staining was employed to observe intracellular lipid levels. The interaction between RP11-817I4.1, miR-3120-3p, and ATP citrate lyase (ACLY) was validated through the performance of dual-luciferase reporter gene and RIP assays.

RESULTS

Three LMR-lncRNAs (negative regulator of antiviral response, RNA transmembrane and coiled-coil domain family 1 antisense RNA 1, and RP11-817I4.1) were identified as predictive markers for HCC patients and were utilized in the construction of risk models. Additionally, proliferation, migration, and invasion were reduced by RP11-817I4.1 knockdown. An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.

CONCLUSION

LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients, and the discovery of a novel LMR-lncRNAs, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

摘要

背景

肝细胞癌(HCC)是最常见的肿瘤类型之一。已发表的研究表明,脂质代谢紊乱对 HCC 的发展有影响。

目的

建立一个与脂质代谢相关的长链非编码 RNA(LMR-lncRNA)的 HCC 预后模型,并深入研究新型 LMR-lncRNA 在 HCC 中的具体作用。

方法

使用癌症基因组图谱数据的相关性和差异表达分析来鉴定差异表达的 LMR-lncRNA。采用实时定量聚合酶链反应分析评估 LMR-lncRNA 的表达。使用尼罗红染色观察细胞内脂质水平。通过双荧光素酶报告基因和 RIP 测定验证 RP11-817I4.1、miR-3120-3p 和三磷酸腺苷柠檬酸裂解酶(ACLY)之间的相互作用。

结果

三种 LMR-lncRNA(抗病毒反应负调控因子、RNA 跨膜和卷曲螺旋域家族 1 反义 RNA 1 和 RP11-817I4.1)被鉴定为 HCC 患者的预测标志物,并用于构建风险模型。此外,RP11-817I4.1 敲低可降低 HCC 细胞的增殖、迁移和侵袭能力。RP11-817I4.1 通过 miR-3120-3p/ACLY 轴显著诱导 HCC 细胞内脂质水平升高。

结论

LMR-lncRNA 能够预测 HCC 患者的临床特征和预后,新型 LMR-lncRNA RP11-817I4.1 的发现揭示了其促进脂质积累的作用,从而加速 HCC 的发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa3/10950635/ece69b1deee2/WJG-30-919-g001.jpg

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