Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis.

Abstract

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.

• Authors: Xiufang Wang, Zhikun Wu, Wenyan Qin, Tong Sun, Senxu Lu, Yalun Li, Yuanhe Wang, Xiaoyun Hu, Dongping Xu, Yutong Wu, Qiuchen Chen, Weifan Yao, Mingyan Liu, Minjie Wei, Huizhe Wu
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 22 Pg. 22656-22687 (11 16 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 33202381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Long Noncoding
• ZFAS1 long non-coding RNA, human
• DNA-Directed RNA Polymerases
• POLR1B protein, human
• DDX21 protein, human
• DEAD-box RNA Helicases

Topics

• Animals
• Apoptosis
• Caco-2 Cells
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (enzymology, genetics, pathology)
• DEAD-box RNA Helicases (genetics, metabolism)
• DNA-Directed RNA Polymerases (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• HT29 Cells
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction
• Tumor Burden