Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis
| Autor: | Senxu Lu, Mingyan Liu, Wenyan Qin, Tong Sun, Weifan Yao, Qiuchen Chen, Huizhe Wu, Minjie Wei, Dongping Xu, Yalun Li, Yuanhe Wang, Zhikun Wu, Yutong Wu, Xiufang Wang, Xiaoyun Hu |
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| Rok vydání: | 2020 |
| Předmět: |
Aging
Colorectal cancer Mice Nude colorectal cancer Apoptosis Biology medicine.disease_cause DEAD-box RNA Helicases Cell Movement medicine Animals Humans CagA Neoplasm Invasiveness lncRNA ZFAS1 Cell Proliferation Mice Inbred BALB C Gene knockdown DDX21 Cell growth POLR1B DNA-Directed RNA Polymerases Cell Biology RNA helicases HCT116 Cells medicine.disease RNA Helicase A Long non-coding RNA Tumor Burden Gene Expression Regulation Neoplastic Cancer research RNA Long Noncoding Caco-2 Cells Colorectal Neoplasms Carcinogenesis HT29 Cells Research Paper Signal Transduction |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Increasing evidence supports long non-coding RNA-ZFAS1 as master protein regulators involved in a variety of human cancers. However, the molecular mechanism is not fully understood in colorectal cancer (CRC) and remains to be elucidated. Here, we uncovered a previously unreported mechanism linking RNA helicase DDX21 regulated by lncRNA ZFAS1 in control of POLR1B expression in CRC initiation and progression. Specifically, ZFAS1 exerted its oncogenic functions and was significantly up-regulated accompanied by elevated DDX21, POLR1B expression in CRC cells and tissues, which further closely associated with poor clinical outcomes. Notably, ZFAS1 knockdown dramatically suppressed CRC cell proliferation, invasion, migration, and increased cell apoptosis, which were contrary to the effect caused by ZFAS1 up-regulation. We further revealed that the inhibitory effect caused by ZFAS1 knockdown could be reversed by DDX21 overexpression in vitro and in vivo. Mechanistically, our research found that ZFAS1 could directly recruit DDX21 protein by harboring the specific motif (AAGA or CAGA). Finally, POLR1B was identified as the downstream target of DDX21 regulated by ZFAS1, which was also up-regulated in CRC cells and tissues and closely related to poor prognosis. The unrecognized ZFAS1/DDX21/POLR1B signaling regulation axis may provide new biomarkers and targets for CRC treatment and prognostic evaluation. |
| Databáze: | OpenAIRE |
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