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Published on: February 5, 2018
RNA helicase DDX5-induced circPHF14 promotes gastric cancer cell progression
Jia Wang1,2, Chunjie Han3, Jinsheng Wang4,5
1Department of Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China.
Abstract:
As a well-established member of a strongly conserved protein family, DDX5 binds to RNA helicase in a specific manner, which can regulate mRNA transcription, protein translation and synthesis and precursor messenger RNA processing or alternative splicing. The effects of DDX5 on carcinogenesis and cancer progression are increasingly evident. Circular RNAs (circRNAs), a novel group of functionally non-coding RNAs (ncRNAs) with disordered expression, are associated with various pathological processes (e.g., tumors). circRNA pattern and its function regulated by DDX5 have not yet been determined. According to our findings, DDX5 was dramatically upregulated for stomach cancer tissues, and its overexpression contributed to the cell growth and invasion of GC cells. Based on the analysis of genome-wide circRNAs conducted with circRNA sequencing, DDX5 induces a large number of circRNAs. Further to screen several circRNAs from PHF14 for function, it was found that circPHF14 was essential for the growth and tumorigenesis of DDX5-positive gastric cancer cells. These findings suggest that in addition to the messenger RNA and microRNA patterns, DDX5 also effects a circRNA pattern, as demonstrated by circPHF14. DDX5-induced circRNAs have been found to be of crucial importance for the growth of DDX5-positive gastric cancer cells, providing a new therapeutic target.
Insights
The RNA helicase DDX5 promotes stomach cancer growth and invasion by upregulating circular RNAs (circRNAs), including circPHF14. This highlights DDX5-induced circRNAs as potential therapeutic targets for gastric cancer.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- DDX5 is a conserved RNA helicase involved in RNA processing and gene expression.
- Dysregulation of DDX5 is linked to various cancers, including gastric cancer (GC).
- Circular RNAs (circRNAs) are emerging as key players in pathological processes, including tumorigenesis.
Purpose of the Study:
- To investigate the role of DDX5 in regulating circRNA expression in gastric cancer.
- To determine the functional significance of DDX5-induced circRNAs in GC cell growth and invasion.
- To identify specific circRNAs regulated by DDX5 in GC.
Main Methods:
- Analysis of DDX5 expression in gastric cancer tissues.
- Genome-wide circRNA sequencing to identify DDX5-regulated circRNAs.
- Functional assays to assess the role of circPHF14 in GC cell growth and tumorigenesis.
Main Results:
- DDX5 was significantly upregulated in gastric cancer tissues and promoted GC cell growth and invasion.
- DDX5 overexpression induced a broad range of circRNAs in GC cells.
- circPHF14 was identified as a key DDX5-induced circRNA essential for the growth and tumorigenesis of DDX5-positive GC cells.
Conclusions:
- DDX5 plays a critical role in gastric cancer progression by modulating the circRNA landscape.
- DDX5-induced circRNAs, exemplified by circPHF14, are crucial for the growth of DDX5-positive gastric cancer.
- Targeting DDX5-regulated circRNAs represents a promising therapeutic strategy for gastric cancer.
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