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
Aims 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. Methods The transcriptome sequencing was used to analy...
| Published in: | PeerJ |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2023-02-01
|
| Subjects: | |
| Online Access: | https://peerj.com/articles/14891.pdf |
| _version_ | 1850037641319284736 |
|---|---|
| author | Peng Zhu Yongyan Pei Jian Yu Wenbin Ding Yun Yang Fuchen Liu Lei Liu Jian Huang Shengxian Yuan Zongyan Wang Fangming Gu Zeya Pan Jinzhong Chen Jinrong Qiu Huiying Liu |
| author_facet | Peng Zhu Yongyan Pei Jian Yu Wenbin Ding Yun Yang Fuchen Liu Lei Liu Jian Huang Shengxian Yuan Zongyan Wang Fangming Gu Zeya Pan Jinzhong Chen Jinrong Qiu Huiying Liu |
| author_sort | Peng Zhu |
| collection | DOAJ |
| container_title | PeerJ |
| description | Aims 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. Methods 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 in vitro. Results 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 in vitro. 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 in vitro. Conclusion 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. |
| format | Article |
| id | doaj-art-deccd58d571a4f6bbc3db255cc76edc7 |
| institution | Directory of Open Access Journals |
| issn | 2167-8359 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| spelling | doaj-art-deccd58d571a4f6bbc3db255cc76edc72025-08-20T00:33:11ZengPeerJ Inc.PeerJ2167-83592023-02-0111e1489110.7717/peerj.14891High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progressionPeng Zhu0Yongyan Pei1Jian Yu2Wenbin Ding3Yun Yang4Fuchen Liu5Lei Liu6Jian Huang7Shengxian Yuan8Zongyan Wang9Fangming Gu10Zeya Pan11Jinzhong Chen12Jinrong Qiu13Huiying Liu14Department of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaSchool of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, Guangdong, ChinaDepartment of General Surgery, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Hepatic Surgery (III), The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Biotherapy, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Biotherapy, The Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaAims 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. Methods 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 in vitro. Results 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 in vitro. 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 in vitro. Conclusion 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.https://peerj.com/articles/14891.pdfLong non-coding RNAHepatocellular carcinomaRNA sequencingProgressionZFAS1/miR-150-5p |
| spellingShingle | Peng Zhu Yongyan Pei Jian Yu Wenbin Ding Yun Yang Fuchen Liu Lei Liu Jian Huang Shengxian Yuan Zongyan Wang Fangming Gu Zeya Pan Jinzhong Chen Jinrong Qiu Huiying Liu 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 Long non-coding RNA Hepatocellular carcinoma RNA sequencing Progression ZFAS1/miR-150-5p |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Long non-coding RNA Hepatocellular carcinoma RNA sequencing Progression ZFAS1/miR-150-5p |
| url | https://peerj.com/articles/14891.pdf |
| work_keys_str_mv | AT pengzhu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT yongyanpei highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT jianyu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT wenbinding highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT yunyang highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT fuchenliu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT leiliu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT jianhuang highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT shengxianyuan highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT zongyanwang highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT fangminggu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT zeyapan highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT jinzhongchen highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT jinrongqiu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression AT huiyingliu highthroughputsequencingapproachfortheidentificationoflncrnabiomarkersinhepatocellularcarcinomaandrevealingtheeffectofzfas1mir1505ponhepatocellularcarcinomaprogression |