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ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3 |
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| Authors: | Gongbao Liu Baihui Liu Xiangqi Liu Lulu Xie Jiajun He Jingjing Zhang Rui Dong Duan Ma Kuiran Dong Mujie Ye |
| Affiliation: | 1. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China;2. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China Contribution: Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Writing - original draft (lead), Writing - review & editing (lead);3. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China Contribution: Validation (equal), Writing - original draft (equal);4. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China Contribution: Resources (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);5. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China Contribution: Resources (supporting), Software (supporting), Visualization (supporting);6. Department of Medical Imaging, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China Contribution: Resources (supporting), Writing - original draft (supporting);7. Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China Contribution: Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);8. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, China |
| Abstract: | It has been becoming increasingly evident that long non-coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome-wide analysis with a lncRNA microarray found that lncRNA HOXA-AS2 was up-regulated in HB. Stable transfected cell lines with HOXA-AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA-AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up-regulation of HOXA-AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA-AS2 was modulated by chromatin remodelling factor ARID1B and transcription co-activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA-AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA-AS2-mediated HB carcinogenesis. In conclusion, HOXA-AS2 is significantly overexpressed in HB and the ARID1B/HOXA-AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy. |
| Keywords: | chromatin remodelling factor hepatoblastoma lncRNA tumorigenesis |