Abstract
BackgroundHPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. The role of testis/cancer antigen in cervical cancer has been revealed. However, there are no reports about the statement of testis/cancer-specific non-coding RNA. In this study, we first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer.MethodsThe specific expression of pseudogenes in each tissue was calculated by “TAU” formula. ROC curve was used to judge the diagnosed value of TCAM1P for high-grade lesions. The proliferation ability of cells was measured by CCK8. The expression of TCAM1P, HPV E6/E7 were detected by qRT-PCR. The binding for RBPs on TCAM1P was predicted by starbase v2.0 database, then RIP assay was used to verify. Besides, Gene Ontology (GO) and KEGG enrichment analysis were performed with “clusterprofiler” R package.ResultsTCAM1P was specifically high-expressed in normal testicular tissue and cervical cancer. Interesting, with the severity of cervical lesions increased, the expression of TCAM1P increased, and TCAM1P could effectively diagnose high-grade cervical lesions. Besides, the expression of TCAM1P was HPV dependent, with highest expression in HPV-positive cervical cancer tissues. Furthermore, RIP assay showed that EIF4A3 regulated the expression of TCAM1P through binding with it. CCK8 assay showed that TCAM1P promoted the proliferation and the Gene ontology (GO) and KEGG Pathway enrichment analysis same suggested that TCAM1P is involved in multiple ways in cell proliferation including Cell cycle, DNA replication and etc.ConclusionsIn this study, we firstly proposed that TCAM1P is cancer/testis pseudogene and is regulated by HPV E6/E7 and EIF4A3. TCAM1P promotes the proliferation of cervical cancer cells and acts as promoter in cervical cancer. Otherwise, TCAM1P promote proliferation through regulating cell cycle and DNA replication, but more evidence needs to be provided to reveal the mechanism by which TCAM1P plays a role in cervical cancer.
Highlights
human papilloma virus (HPV) as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated
Guanylate binding protein 1 pseudogene 1 (GBP1P1) and pituitary tumor-transforming 3 pseudogene (PTTG3P), were over-expressed in cervical cancer and PTTG3P was positively correlated with PTTG1 levels, which promote cervical cancer cells proliferation through cyclin B1 (CCNB) and increased CC cell invasiveness through upregulation of snail family transcriptional repressor 1 (SNAIL) and downregulation of E-cadherin [8, 9]
The identification of cancer/testis (CT) pseudogenes Testicular cell adhesion molecule 1 (TCAM1P) in cervical cancer First, we screened out all pseudogenes based on the current human pseudogene annotation in HUGO gene nomenclature committee (HGNC, https://www.genenames.org/)
Summary
HPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. We first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer. Interesting, at present, the activity of non-coding RNA in tumorigenesis is increasingly revealed, and more and more evidences suggest its important role in tumors [4–7], including the role of pseudogenes in cervical cancer. We speculated whether there are pseudogenes expressed in tumors and testicular tissues, and can be used as screening targets and therapeutic targets
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