FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated death worldwide. Indeed, despite the benefit of sorafenib in the treatment of some patients with HCC, the majority of these patients have a poor response to or intolerance of sorafenib, resulting in further tumor progres...
| 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/S2162253119300812 |
| _version_ | 1818414144017137664 |
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| author | Yingru Zhi Mubalake Abudoureyimu Hao Zhou Ting Wang Bing Feng Rui Wang Xiaoyuan Chu |
| author_facet | Yingru Zhi Mubalake Abudoureyimu Hao Zhou Ting Wang Bing Feng Rui Wang Xiaoyuan Chu |
| author_sort | Yingru Zhi |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated death worldwide. Indeed, despite the benefit of sorafenib in the treatment of some patients with HCC, the majority of these patients have a poor response to or intolerance of sorafenib, resulting in further tumor progression. Exploring the mechanisms underlying sorafenib resistance is essential to the treatment of HCC. Long noncoding RNAs (lncRNAs) are known as participants in tumorigenesis. In this study, we identified that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR), was upregulated in HCC cell lines, which was transcriptionally activated by FOXM1. Furthermore, the sponging of miR-876-5p by LINC-ROR released FOXM1, thereby forming a positive-feedback loop. Additionally, we demonstrated that upregulation of both FOXM1 and LINC-ROR impaired the sensitivity to sorafenib in HCC cells. The role of this feedback loop was demonstrated by rescue assays. These results revealed a novel molecular feedback loop between LINC-ROR and FOXM1 and elucidated their functions in sorafenib sensitivity of HCC cell lines. Keywords: LINC-ROR, FOXM1, miR-876-5p, HCC, sorafenib, sensitivity |
| first_indexed | 2024-12-14T11:14:25Z |
| format | Article |
| id | doaj.art-92f55a1e726b4a6f950e27c5c15452fe |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-14T11:14:25Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-92f55a1e726b4a6f950e27c5c15452fe2022-12-21T23:04:06ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-06-0116576588FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular CarcinomaYingru Zhi0Mubalake Abudoureyimu1Hao Zhou2Ting Wang3Bing Feng4Rui Wang5Xiaoyuan Chu6Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of ChinaDepartment of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of ChinaDepartment of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaDepartment of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of ChinaDepartment of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of ChinaDepartment of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China; Corresponding author: Rui Wang, Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu Province, People’s Republic of China.Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of ChinaHepatocellular carcinoma (HCC) is the second leading cause of cancer-associated death worldwide. Indeed, despite the benefit of sorafenib in the treatment of some patients with HCC, the majority of these patients have a poor response to or intolerance of sorafenib, resulting in further tumor progression. Exploring the mechanisms underlying sorafenib resistance is essential to the treatment of HCC. Long noncoding RNAs (lncRNAs) are known as participants in tumorigenesis. In this study, we identified that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR), was upregulated in HCC cell lines, which was transcriptionally activated by FOXM1. Furthermore, the sponging of miR-876-5p by LINC-ROR released FOXM1, thereby forming a positive-feedback loop. Additionally, we demonstrated that upregulation of both FOXM1 and LINC-ROR impaired the sensitivity to sorafenib in HCC cells. The role of this feedback loop was demonstrated by rescue assays. These results revealed a novel molecular feedback loop between LINC-ROR and FOXM1 and elucidated their functions in sorafenib sensitivity of HCC cell lines. Keywords: LINC-ROR, FOXM1, miR-876-5p, HCC, sorafenib, sensitivityhttp://www.sciencedirect.com/science/article/pii/S2162253119300812 |
| spellingShingle | Yingru Zhi Mubalake Abudoureyimu Hao Zhou Ting Wang Bing Feng Rui Wang Xiaoyuan Chu FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma Molecular Therapy: Nucleic Acids |
| title | FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma |
| title_full | FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma |
| title_fullStr | FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma |
| title_full_unstemmed | FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma |
| title_short | FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma |
| title_sort | foxm1 mediated linc ror regulates the proliferation and sensitivity to sorafenib in hepatocellular carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119300812 |
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