High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression

To screen abnormal lncRNAs and diagnostic biomarkers in the progression of hepatocellular carcinoma through high-throughput sequencing and explore the underlying mechanisms of abnormal lncRNAs in the progression of hepatocellular carcinoma. The transcriptome sequencing was used to analyze the RNA ex...

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Published in:	PeerJ (San Francisco, CA) CA), 2023-02, Vol.11, p.e14891, Article e14891
Main Authors:	Zhu, Peng, Pei, Yongyan, Yu, Jian, Ding, Wenbin, Yang, Yun, Liu, Fuchen, Liu, Lei, Huang, Jian, Yuan, Shengxian, Wang, Zongyan, Gu, Fangming, Pan, Zeya, Chen, Jinzhong, Qiu, Jinrong, Liu, Huiying
Format:	Article
Language:	eng
Subjects:	Biological markers Biomarkers Carcinoma, Hepatocellular - genetics Cell differentiation Cell migration Cell proliferation Development and progression Diagnosis Gastroenterology and Hepatology Genes Hepatocellular carcinoma Hepatoma High-Throughput Nucleotide Sequencing Humans Immune response Liver cancer Liver Neoplasms - genetics Long non-coding RNA Medical prognosis Medical research MicroRNA MicroRNAs MicroRNAs - genetics miRNA Molecular Biology Next-generation sequencing Non-coding RNA Oncology Progression Risk assessment RNA sequencing RNA, Long Noncoding - genetics Survival analysis Transcriptomes Tumors ZFAS1/miR-150-5p
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Summary:	To screen abnormal lncRNAs and diagnostic biomarkers in the progression of hepatocellular carcinoma through high-throughput sequencing and explore the underlying mechanisms of abnormal lncRNAs in the progression of hepatocellular carcinoma. The transcriptome sequencing was used to analyze the RNA expression profile and identify differentially expressed RNAs. Hub lncRNAs were screened by combining (WGCNA, ceRNA regulatory network, PPI, GO and KEGG analyses, Kaplan-Meier curve analysis, Cox analysis, risk model construction and qPCR). Thereafter, the correlation between the expression of hub lncRNAs and tumor clinicopathological parameters was analyzed, and the hub lncRNAs were analyzed by GSEA. Finally, the effects of hub RNAs on the proliferation, migration and invasion of HepG2 cells were investigated . Compared with the control group, a total of 610 lncRNAs, 2,593 mRNAs and 26 miRNAs were screened in patients with hepatocellular carcinoma. Through miRNA target prediction and WGCNA, a ceRNA was constructed, comprising 324 nodes and 621 edges. Enrichment analysis showed that mRNAs in ceRNA were involved mainly in cancer development progression. Then, the ZFAS1/miR-150-5p interaction pair was screened out by Kaplan Meier curve analysis, Cox analysis and qPCR analysis. Its expression was related to tumor stage, TNM stage and patient age. ROC curve analysis showed that it has a good predictive value for the risk of hepatocellular carcinoma. GSEA showed that ZFAS1 was also enriched in the regulation of immune response, cell differentiation and proliferation. Loss-of-function experiments revealed that ZFAS1 inhibition could remarkably suppress HepG2 cell proliferation, migration and invasion . Bioinformatic analysis and luciferase reporter assays revealed that ZFAS1 directly interacted with miR-150-5p. Rescue experiments showed that a miR-150-5p inhibitor reversed the cell proliferation, migration and invasion functions of ZFAS1 knockdown . ZFAS1 is associated with the malignant status and prognosis of patients with hepatocellular carcinoma, and the ZFAS1/miR-150-5p axis is involved in hepatocellular carcinoma progression.
ISSN:	2167-8359 2167-8359