LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation
| العنوان: | LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation |
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| المؤلفون: | Jia-Jia Zhou, Di Cheng, Junge Deng, Xiao-Yu He, Bin Zhang, Zhe Meng, Xiao-Geng Deng, Guolin Li, Huilin Ye, Rufu Chen, Shangyou Zheng, Lusheng Wei |
| المصدر: | EBioMedicine |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Research paper, Hepatocellular carcinoma, Epigenesis, Genetic, lncRNA, long non-coding RNA, Mice, 0302 clinical medicine, Cell Movement, EZH2, Enhancer of zeste homolog 2, MiR-122, Promoter Regions, Genetic, CCNG1, Cyclin G1, Gene knockdown, DNA methylation, Cell Cycle, Liver Neoplasms, EZH2, HOTAIR, General Medicine, HOTAIR, Homeobox transcript antisense intergenic RNA, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Female, RNA Interference, RNA, Long Noncoding, Epigenetics, Carcinoma, Hepatocellular, Cyclin G1, Biology, Models, Biological, DNA methyltransferase, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Cell Line, Tumor, microRNA, Animals, Humans, Cell Proliferation, Base Sequence, miR-122, microRNA-122, microRNA-122, LncRNA HOTAIR, Xenograft Model Antitumor Assays, Disease Models, Animal, MicroRNAs, 030104 developmental biology, DNMT, DNA methyltransferase, Cancer research, HCC, hepatocellular carcinoma |
| الوصف: | Background MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in multiple cancers including HCC. However, the relationship between HOTAIR and miR-122 in HCC remains largely unknown. Methods We investigated the function of HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory network between HOTAIR and miR-122 was further detected following overexpression or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. Findings In this study, we found that HOTAIR was highly expressed whereas miR-122 was suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell proliferation and induced cell cycle arrest in vitro and suppressed tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG island was located in the miR-122 promoter region. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover, HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122 induced by HOTAIR directly reactivated oncogene Cyclin G1 expression. Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122 expression via DNA methylation, leading to activation of Cyclin G1 and promotion of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR-mediated hepatocarcinogenesis via suppressing miR-122. Highlights • HOTAIR is highly expressed in HCC, and negatively regulates miR-122 expression in HCC cells. • HOTAIR increased HCC cell proliferation and tumor growth through downregulating miR-122 expression. • HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. • HOTAIR upregulated DNMTs expression via EZH2. • HOTAIR increased cyclin G1 expression through repressing miR-122. |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b62d90e88a368d9012d4535bc2eb5175Test https://doi.org/10.1016/j.ebiom.2018.08.055Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b62d90e88a368d9012d4535bc2eb5175 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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