A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways
Long noncoding RNAs (lncRNAs) are involved in a variety of biological processes such as tumor proliferation and metastasis. A close relationship between hepatitis B virus X protein (HBx) and SMYD3 in promoting the proliferation and metastasis of hepatocellular carcinoma (HCC) was recently reported....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119300940 |
| _version_ | 1818932163427434496 |
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| author | Zheng Chen Wei Yu Qiming Zhou Jianlong Zhang Hai Jiang Dake Hao Jie Wang Zhenyu Zhou Chuanchao He Zhiyu Xiao |
| author_facet | Zheng Chen Wei Yu Qiming Zhou Jianlong Zhang Hai Jiang Dake Hao Jie Wang Zhenyu Zhou Chuanchao He Zhiyu Xiao |
| author_sort | Zheng Chen |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) are involved in a variety of biological processes such as tumor proliferation and metastasis. A close relationship between hepatitis B virus X protein (HBx) and SMYD3 in promoting the proliferation and metastasis of hepatocellular carcinoma (HCC) was recently reported. However, the exact oncogenic mechanism of HBx-SMYD3 remains unknown. In this study, by performing lncRNA microarray analysis, we identified a novel lncRNA that was regulated by both HBx and SMYD3, and we named it lncIHS (lncRNA intersection between HBx microarray and SMYD3 microarray). lncIHS was overexpressed in HCC and decreased the survival rate of HCC patients. Knockdown of lncIHS inhibited HCC cell migration, invasion, and proliferation, and vice versa. Further study showed that lncIHS positively regulated the expression of epithelial mesenchymal transition (EMT)-related markers c-Myc and Cyclin D1, as well as the activation of the ERK- and AKT-signaling pathways. lncIHS exerted its oncogenic effect through ERK and AKT signaling. Moreover, results from transcriptome-sequencing analysis and mass spectrometry showed that lncIHS regulated multiple genes that were the upstream molecules of the ERK- and AKT-signaling pathways. Therefore, our findings suggest a regulatory network of ERK and AKT signaling through lncIHS, which is downstream of HBx-SMYD3, and they indicate that lncIHS may be a potential target for treating HCC. Keywords: hepatocellular carcinoma, SMYD3, lncRNA-HIS, DUSP5, DUSP10, MAP3K8, ERK, AKT, metastasis, proliferation |
| first_indexed | 2024-12-20T04:28:07Z |
| format | Article |
| id | doaj.art-621406289a804c85ae645b089135681d |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T04:28:07Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-621406289a804c85ae645b089135681d2022-12-21T19:53:27ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-06-0116707720A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling PathwaysZheng Chen0Wei Yu1Qiming Zhou2Jianlong Zhang3Hai Jiang4Dake Hao5Jie Wang6Zhenyu Zhou7Chuanchao He8Zhiyu Xiao9Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaSurgical Bioengineering Laboratory, Department of Surgery, School of Medicine, University of California, Davis, Sacramento, CA 95817, USAGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Corresponding author: Zhenyu Zhou, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 33 Yingfeng Road, Guangzhou 510120, China.Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Corresponding author: Chuanchao He, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 33 Yingfeng Road, Guangzhou 510120, China.Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Corresponding author: Zhiyu Xiao, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 33 Yingfeng Road, Guangzhou 510120, China.Long noncoding RNAs (lncRNAs) are involved in a variety of biological processes such as tumor proliferation and metastasis. A close relationship between hepatitis B virus X protein (HBx) and SMYD3 in promoting the proliferation and metastasis of hepatocellular carcinoma (HCC) was recently reported. However, the exact oncogenic mechanism of HBx-SMYD3 remains unknown. In this study, by performing lncRNA microarray analysis, we identified a novel lncRNA that was regulated by both HBx and SMYD3, and we named it lncIHS (lncRNA intersection between HBx microarray and SMYD3 microarray). lncIHS was overexpressed in HCC and decreased the survival rate of HCC patients. Knockdown of lncIHS inhibited HCC cell migration, invasion, and proliferation, and vice versa. Further study showed that lncIHS positively regulated the expression of epithelial mesenchymal transition (EMT)-related markers c-Myc and Cyclin D1, as well as the activation of the ERK- and AKT-signaling pathways. lncIHS exerted its oncogenic effect through ERK and AKT signaling. Moreover, results from transcriptome-sequencing analysis and mass spectrometry showed that lncIHS regulated multiple genes that were the upstream molecules of the ERK- and AKT-signaling pathways. Therefore, our findings suggest a regulatory network of ERK and AKT signaling through lncIHS, which is downstream of HBx-SMYD3, and they indicate that lncIHS may be a potential target for treating HCC. Keywords: hepatocellular carcinoma, SMYD3, lncRNA-HIS, DUSP5, DUSP10, MAP3K8, ERK, AKT, metastasis, proliferationhttp://www.sciencedirect.com/science/article/pii/S2162253119300940 |
| spellingShingle | Zheng Chen Wei Yu Qiming Zhou Jianlong Zhang Hai Jiang Dake Hao Jie Wang Zhenyu Zhou Chuanchao He Zhiyu Xiao A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways Molecular Therapy: Nucleic Acids |
| title | A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways |
| title_full | A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways |
| title_fullStr | A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways |
| title_full_unstemmed | A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways |
| title_short | A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways |
| title_sort | novel lncrna ihs promotes tumor proliferation and metastasis in hcc by regulating the erk and akt gsk 3β signaling pathways |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119300940 |
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