Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma
Abstract Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expressi...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-020-01664-1 |
| _version_ | 1831789277438017536 |
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| author | Hui He Yawei Wang Peng Ye Dehui Yi Ying Cheng Haibo Tang Zhi Zhu Xun Wang Shi Jin |
| author_facet | Hui He Yawei Wang Peng Ye Dehui Yi Ying Cheng Haibo Tang Zhi Zhu Xun Wang Shi Jin |
| author_sort | Hui He |
| collection | DOAJ |
| description | Abstract Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. Results The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. Conclusions ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC. |
| first_indexed | 2024-12-22T14:06:13Z |
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| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-22T14:06:13Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-3c07fd5ef2b1489e9218c2c5bedbdcc72022-12-21T18:23:17ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-08-0139111710.1186/s13046-020-01664-1Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinomaHui He0Yawei Wang1Peng Ye2Dehui Yi3Ying Cheng4Haibo Tang5Zhi Zhu6Xun Wang7Shi Jin8Department of Laparoscopic Surgery, the First Affiliated Hospital of Dalian Medical UniversityDepartment of thoracic surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital& InstituteDepartment of Urological Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of organ transplantation& hepatobiliary surgery, the First Affiliated Hospital of China Medical UniversityDepartment of organ transplantation& hepatobiliary surgery, the First Affiliated Hospital of China Medical UniversityDepartment of Gastrointestinal & Hernia & Bariatric Surgery, the Third Xiangya Hospital of Central South UniversityDepartment of Laparoscopic Surgery, the First Affiliated Hospital of Dalian Medical UniversityDepartment of Laparoscopic Surgery, the First Affiliated Hospital of Dalian Medical UniversityDepartment of Laparoscopic Surgery, the First Affiliated Hospital of Dalian Medical UniversityAbstract Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. Results The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. Conclusions ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.http://link.springer.com/article/10.1186/s13046-020-01664-1LncRNA ZFPM2-AS1miR-139Liver hepatocellular carcinomaTCGABioinformatics analysis |
| spellingShingle | Hui He Yawei Wang Peng Ye Dehui Yi Ying Cheng Haibo Tang Zhi Zhu Xun Wang Shi Jin Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma Journal of Experimental & Clinical Cancer Research LncRNA ZFPM2-AS1 miR-139 Liver hepatocellular carcinoma TCGA Bioinformatics analysis |
| title | Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma |
| title_full | Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma |
| title_fullStr | Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma |
| title_full_unstemmed | Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma |
| title_short | Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma |
| title_sort | long noncoding rna zfpm2 as1 acts as a mirna sponge and promotes cell invasion through regulation of mir 139 gdf10 in hepatocellular carcinoma |
| topic | LncRNA ZFPM2-AS1 miR-139 Liver hepatocellular carcinoma TCGA Bioinformatics analysis |
| url | http://link.springer.com/article/10.1186/s13046-020-01664-1 |
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