AUTHOR=Zhang Yeqian , Yu Fengrong , Ni Bo , Li Qing , Bae Seong-Woo , Choi Jong-Ho , Yang Han-Kwang , Kong Seong-Ho , Zhu Chunchao 

TITLE=The RNA-Binding Protein DDX18 Promotes Gastric Cancer by Affecting the Maturation of MicroRNA-21

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.598238

DOI=10.3389/fonc.2020.598238

ISSN=2234-943X

ABSTRACT=OBJECTIVES: The ncRNAs are playing important roles in GC. Most studies focused on the functions and influence of ncRNAs, but seldom on their maturation. DDX genes are a family of RNA binding proteins that may work on the development of ncRNAs. By TCGA data and our cohort, we aimed to find some GC related genes. We evaluated the clinical significance and prognostic value of DDX18, which is overexpressed in GC tissues. For the development of new therapeutic targets for the treatment of GC, we investigated its effect on the malignant biological behavior of GC in vitro and in vivo, also discussed its mechanism.
METHODS: (1) By combining with TCGA data and our cohort, we finally filtered out DDX18 upregulated in GC tissues for further investigation. (2) The protein expression of DDX18 was detected by IHC. Then the relationship between DDX18 expression level and clinicalpathological data and prognosis was analyzed. (3) CCK-8 assay and colony formation assay experiments were used to evaluate the effect of DDX18 on cell growth and proliferation in vitro. Transwell assay was also performed to examine migration and invasion of GC cells. Cell apoptosis experiment was analyzed by using Annexin V/PI. We also established the gastric cancer xenografts subcutaneous model. co-IP、small RNAseq and western blot were performed to explore the mechanism of DDX18 and GC. PDX model were used to confirmed the effect of DDX18 in GC tissues. 
RESULT: (1) DDX18 was upregulated in GC tissues of TCGA database and our cohort. The expression of DDX18 was also closely related with tumor volumn, Borramn classification, degree of tumor differentiation, cancer embolus, lymph node metastasis, and TNM stage.(3)DDX18 could promote cell proliferation, migration and invasion, and inhibit cell apoptosis in vivo and in vitro; (4)DDX18 could promote the maturation of miRNA-21 through direct interaction with Drosha, decreasing PTEN, regulating the AKT signaling pathway. (5)PDX model showed that DDX18 could promote the proliferation of GC tissues by PTEN-AKT signaling pathway. 
CONCLUSIONS: (1) DDX18 can be treated as molecular markers to assess the prognosis of gastric cancer patients. (2) DDX18 could be a potential therapeutic target towards gastric cancer.