DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35

Xin Zhou; Zhihong Liu; Tengfei He; Cuifeng Zhang; Manman Jiang; Yuxiao Jin; Ziyu Wu; Changji Gu; Wei Zhang; Xiaodong Yang

doi:10.1186/s12935-022-02478-1

DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35

Cancer Cell Int. 2022 Feb 2;22(1):58. doi: 10.1186/s12935-022-02478-1.

Authors

Xin Zhou^#¹, Zhihong Liu^#¹, Tengfei He¹, Cuifeng Zhang¹, Manman Jiang², Yuxiao Jin¹, Ziyu Wu¹, Changji Gu¹, Wei Zhang³, Xiaodong Yang⁴

Affiliations

¹ Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China.
² Soochow University, 1 Shizi Street, Suzhou, China.
³ Department of Radiotherapy, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China. zhangweiszjs@163.com.
⁴ Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China. 20194233020@stu.suda.edu.cn.

^# Contributed equally.

Abstract

Background: Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.

Methods: In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC-MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR.

Results: In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC-MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC.

Conclusions: In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.

Keywords: Colorectal cancer; DEAD-box helicase 10 (DDX10); Oncogene; RPL35; mRNA splicing.