In silico analysis of DND1 and its co-expressed genes in human cancers

Yun Zhang; Yafang Li; Dhruv Chachad; Bin Liu; Jyotsna D Godavarthi; Abie Williams-Villalobo; Latifat Lasisi; Shunbin Xiong; Angabin Matin

doi:10.1016/j.bbrep.2022.101206

In silico analysis of DND1 and its co-expressed genes in human cancers

Biochem Biophys Rep. 2022 Jan 13:29:101206. doi: 10.1016/j.bbrep.2022.101206. eCollection 2022 Mar.

Authors

Yun Zhang¹, Yafang Li², Dhruv Chachad³, Bin Liu⁴, Jyotsna D Godavarthi¹, Abie Williams-Villalobo¹, Latifat Lasisi¹, Shunbin Xiong³, Angabin Matin⁵

Affiliations

¹ Department of Pharmaceutical Sciences, Joan M. Lafleur College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, 77004, USA.
² Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
³ Department of Genetics, MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁴ Department of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁵ Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, 31207, USA.

Abstract

Dead-End (DND1) is an RNA-binding protein involved in translational regulation. Defects in DND1 gene causes germ cell tumors and sterility in rodents. Experimental studies with human somatic cancer cells indicate that DND1 has anti-proliferative and pro-apoptotic function in some while oncogenic function in other cells. We examined The Cancer Genome Atlas data for gene alterations and gene expression changes in DND1 in a variety of human cancers. We found that DND1 is amplified, deleted or mutated in multiple human cancers. In different cancers, DND1 alteration correlates with increased diagnosis age of patients, shift in tumor spectrum or change of tumor sites and in some cases is significantly associated with worse survival for cancer patients. For 15 cancers, we retrieved expression data of thousands of genes that co-expressed with DND1. We found that these cancers contain different percentage of genes that are positively or negatively co-expressed with DND1. Ingenuity Pathway Analysis was performed to explore the biological implications of these genes. More than 10 canonical pathways were identified and each cancer type exhibits unique pathway profiles. Comparison analysis across all 15 cancer types showed that some cancers exhibit strikingly similar profiles of DND1-correlated signaling pathway activation or suppression. Our data reinforce the notion that the biological role of DND1 is cell-type specific and suggest that DND1 may play opposing role by exerting anti-proliferative effects in some cancer cells while being pro-proliferative in others. Our study provides valuable insights to direct experimental investigations of DND1 function in somatic cancers.

Keywords: Co-expression; DND1; IPA; Somatic cancers; TCGA.