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

Aging
Xiufang WangHuizhe Wu

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 rela...Continue Reading

Citations

Aug 14, 2021·Journal of Evidence-based Integrative Medicine·Melody HermelJames Gray

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Datasets Mentioned

BETA
GSE137511

Methods Mentioned

BETA
Trans-well
Flow cytometry
pull down
CLIP
pull-down
RNA-seq
xenografts
xenograft
transfection
PCR

Software Mentioned

MOE
SPSS
Ensembl
STRING
Genesrping
Affymetrix

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