Pseudogene Transcripts in Head and Neck Cancer: Literature Review and In Silico Analysis

Abstract

Once considered nonfunctional, pseudogene transcripts are now known to provide valuable information for cancer susceptibility, including head and neck cancer (HNC), a serious health problem worldwide, with about 50% unimproved overall survival over the last decades. The present review focuses on the role of pseudogene transcripts involved in HNC risk and prognosis. We combined current literature and in silico analyses from The Cancer Genome Atlas (TCGA) database to identify the most deregulated pseudogene transcripts in HNC and their genetic variations. We then built a co-expression network and performed gene ontology enrichment analysis to better understand the pseudogenes’ interactions and pathways in HNC. In the literature, few pseudogenes have been studied in HNC. Our in silico analysis identified 370 pseudogene transcripts associated with HNC, where SPATA31D5P, HERC2P3, SPATA31C2, MAGEB6P1, SLC25A51P1, BAGE2, DNM1P47, SPATA31C1, ZNF733P and OR2W5 were found to be the most deregulated and presented several genetic alterations. NBPF25P, HSP90AB2P, ZNF658B and DPY19L2P3 pseudogenes were predicted to interact with 12 genes known to participate in HNC, DNM1P47 was predicted to interact with the TP53 gene, and HLA-H pseudogene was predicted to interact with HLA-A and HLA-B genes. The identified pseudogenes were associated with cancer biology pathways involving cell communication, response to stress, cell death, regulation of the immune system, regulation of gene expression, and Wnt signaling. Finally, we assessed the prognostic values of the pseudogenes with the Kaplan–Meier Plotter database, and found that expression of SPATA31D5P, SPATA31C2, BAGE2, SPATA31C1, ZNF733P and OR2W5 pseudogenes were associated with patients’ survival. Due to pseudogene transcripts’ potential for cancer diagnosis, progression, and as therapeutic targets, our study can guide new research to HNC understanding and development of new target therapies.

Association of Inherited Copy Number Variation in ADAM3A and ADAM5 Pseudogenes with Oropharynx Cancer Risk and Outcome

“…ADAM3A and ADAM5 are classified as pseudogenes once they do not seem to produce a specific protein [ 40 ]. The prevalent existence of pseudogenes indicates that they may play a key role in basic physiology and disease progression, including that of cancer [ 22 , 41 ]. The ways in which ADAM3A and ADAM5 may mediate tumorigenesis in OPSCC are still unclear, but pseudogenes can interact with parental genes or other gene loci, altering their sequences and/or transcriptional activities [ 41 ].…”

“…However, thanks to advancements in genomics research, they are now recognized to regulate gene expression [ 21 ]. Pseudogene-derived transcripts, containing microRNA(miRNA)-binding elements, can exert the regulatory control of ancestral or other genes’ expression levels by competing for miRNAs, acting as critical modulators in cancer development and progression [ 21 , 22 ].…”

Non-Coding RNAs in Human Health and Diseases

“…This paper provides a comprehensive table of databases and other resources for ceRNAs that would be a great starting place for individuals thinking about the ceRNA network in their tissue or disease of interest. In the last section of their review, Ye and colleagues discuss the role of pseudogenes as ceRNAs, which directly leads to our last paper to be discussed by Carron and colleagues [52]. This paper reviews the plausible role of pseudogene transcripts, which are classified as ncRNA precisely because they have degenerated to the point where no proteins are made from the duplicated gene transcript, and often negatively regulate the sense RNA from the parental genes (Figure 4).…”

Pseudogenes in Cancer: State of the Art

“…For example, Carron, Coletta, and Lourenço conducted an analysis focused on GCNs of pseudogenes in a head and neck cancer (HNC) dataset [ 125 ]. By employing a pipeline designed to identify cancer-relevant pseudogene interactions, they discovered several modules comprising protein-coding genes and pseudogenes.…”

“…Notably, these modules contained genes associated with carcinogenesis, cell cycle regulation, and immune response. In one instance, the cell cycle module included the pseudogene DNM1P47 and the gene TP53, suggesting an indirect interaction between these transcripts in HNC [ 125 ].…”