LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia
| العنوان: | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
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| المؤلفون: | Yafeng Jiang, Guangsen Zhang, Yujiao Luo, Hongling Peng, Shangjie Wu, Piao Hu, Yewei Wang, Doudou Tang |
| المصدر: | Cell Death and Disease, Vol 12, Iss 9, Pp 1-10 (2021) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Acute promyelocytic leukemia, Transcriptional Activation, Cancer Research, Immunology, MAP Kinase Kinase Kinase 1, Biology, medicine.disease_cause, Models, Biological, Article, Acute myeloid leukaemia, Proto-Oncogene Proteins c-myc, Cellular and Molecular Neuroscience, Downregulation and upregulation, Leukemia, Promyelocytic, Acute, immune system diseases, Cell Line, Tumor, Enzyme Stability, medicine, Gene silencing, Humans, RNA, Messenger, RNA, Small Interfering, neoplasms, Cell Proliferation, Cell Nucleus, Gene knockdown, QH573-671, Cell growth, Gene Expression Regulation, Leukemic, Cell Biology, medicine.disease, Potassium Channels, Voltage-Gated, Cancer cell, Cancer research, RNA-Binding Protein FUS, Carcinogenesis, Cytology, Protein Binding |
| الوصف: | Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1 is found to contribute to carcinogenesis, but its role in acute promyelocytic leukemia (APL) is unclear. In this study, by analyzing data from Gene Expression Omnibus, The Cancer Genome Atlas database and our clinical samples, we found that KCNQ1OT1 was selectively highly expressed in APL. Functional assays demonstrated that knockdown of KCNQ1OT1 reduced APL cell proliferation and increased apoptosis. Further evidence showed that KCNQ1OT1 was mainly located in the cytoplasm of APL patient-derived NB4 cells and APL patient bone marrow samples. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA. Whereas KCNQ1OT1 and FUS did not affect each other. Importantly, knockdown of MAP3K1 impaired APL cell proliferation. Finally, c-Myc transactivated KCNQ1OT1 in APL cells through binding to its promoter while knockdown of c-Myc decreased KCNQ1OT1 expression. Our results not only revealed that c-Myc transactivated KCNQ1OT1 and upregulated KCNQ1OT1 promoted APL cell proliferation, but also demonstrated that KCNQ1OT1 bound to FUS to synergistically stabilize MAP3K1 mRNA, thus facilitating APL cell proliferation. This study established a previously unidentified role of KCNQ1OT1 in the development of APL, and KCNQ1OT1 may serve as a potential therapeutic target for APL. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc93ff0af52a0b8c1edaed162eab8a8d https://doaj.org/article/cd9954d0320943f5a1fa60b997a28383 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fc93ff0af52a0b8c1edaed162eab8a8d |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20414889 |
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