A Novel lncRNA lncRNA-4045 Promotes the Progression of Hepatocellular Carcinoma by Affecting the Expression of AKR1B10

Chao Tan; Xi Zeng; Xuefeng Guo; Meile Mo; Xiaoyun Ma; Bihu Liu; Shun Liu; Xiaoyun Zeng; Dongping Huang; Xiaoqiang Qiu

doi:10.1007/s10620-024-08383-z

A Novel lncRNA lncRNA-4045 Promotes the Progression of Hepatocellular Carcinoma by Affecting the Expression of AKR1B10

Dig Dis Sci. 2024 Apr 25. doi: 10.1007/s10620-024-08383-z. Online ahead of print.

Authors

Chao Tan^#¹, Xi Zeng^#², Xuefeng Guo¹, Meile Mo³, Xiaoyun Ma³, Bihu Liu³, Shun Liu³, Xiaoyun Zeng¹, Dongping Huang³, Xiaoqiang Qiu⁴

Affiliations

¹ Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Zhiyuan Road, Guilin, 541199, Guangxi, People's Republic of China.
² Department of Occupational and Environmental Health, School of Public Health, Guilin Medical University, Zhiyuan Road, Guilin, 541199, Guangxi, People's Republic of China.
³ Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
⁴ Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China. qiuxiaoqiang@gxmu.edu.cn.

^# Contributed equally.

PMID: 38662158
DOI: 10.1007/s10620-024-08383-z

Abstract

Background: Long noncoding RNAs (lncRNAs) have been shown to be related to the occurrence and development of a variety of cancers including hepatocellular carcinoma (HCC). However, a large number of potential HCC-related lncRNAs remain undiscovered and are yet to be fully understood.

Methods: Differentially expressed lncRNAs were first obtained from the tumor tissues and adjacent normal tissues of five HCC patients using high-throughput microarray chips. Then the expression levels of 10 differentially expressed lncRNAs were verified in 50 pairs of tissue samples from patients with HCC by quantitative real-time PCR (qRT-PCR). The oncogenic effects of lncRNA-4045 (ENST00000524045.6) in HCC cell lines were verified through a series of in vitro experiments including CCK-8 assay, plate clone formation assay, transwell assay, scratch assay, and flow cytometry. Subsequently, the potential target genes of lncRNA-4045 were predicted by bioinformatics analysis, fluorescence in situ hybridization assay, and RNA sequencing. The mechanism of lncRNA-4045 in HCC was explored by WB assay as well as rescue and enhancement experiments.

Results: The results from microarray chips showed 1,708 lncRNAs to have been significantly upregulated and 2725 lncRNAs to have been significantly downregulated in HCC tissues. Via validation in 50 HCC patients, a novel lncRNA lncRNA-4045 was found significantly upregulated in HCC tissues. Additionally, a series of in vitro experiments showed that lncRNA-4045 promoted the proliferation, invasion, and migration of HCC cell lines, and inhibited the apoptosis of HCC cell lines. The results of qRT-PCR in HCC tissues showed that the expression levels of AKR1B10 were significantly positively correlated with lncRNA-4045. LncRNA-4045 knockdown significantly down-regulated AKR1B10 protein expression, and overexpression of lncRNA-4045 led to significant up-regulation of AKR1B10 protein in HCC cell lines. Lastly, down-regulation of AKR1B10 could partially eliminate the enhancement of cell proliferation induced by lncRNA-4045 overexpression, while up-regulation of AKR1B10 was shown to enhance those effects.

Conclusion: LncRNA-4045 may promote HCC via enhancement of the expression of AKR1B10 protein.

Keywords: AKR1B10; Hepatocellular carcinoma; Long noncoding RNA; lncRNA-4045.