Abstract
The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.
Highlights
Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries [1]
Similar dysregulated expression patterns of most Transcription factors (TFs) were in cancer tissues from 306 samples of TCGA-CESC ( e Cancer Genome Atlas-Cervical Squamous Cell Carcinoma) and 13 matched normal tissues from GTEx
In cervical cancer, human papilloma virus (HPV)-18 E6induced PDZRN3 degradation can lead to an increase in STAT5 activation [16]. rough PDZRN3, it would be interesting to see if EMX2 affects the Wnt/-catenin pathway and STAT5 in cervical cancer
Summary
Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries [1]. Differential expressions were further validated in GEPIA (Gene Expression Profiling Interactive Analysis) [15] Among those DEGs, five homeoboxcontaining TFs (EMX2, HOXC6, ISL1, HOPX, and MSX1) were dysregulated in cervical cancer, indicating their particular involvement in cervical cancer tumorigenesis. We showed that EMX2 might be a direct upstream regulator of PDZRN3 (PDZ Domain Containing Ring Finger 3) Previous study showed it was a target of human papillomavirus type 16 (HPV-16) and HPV-18 E6 in cervical cancer [16]. E GEPIA (Gene Expression Profiling Interactive Analysis) is an interactive web server containing the sequenced RNA expression data of 9736 tumors and 8587 normal samples from both the TCGA and GTEx (the Genotype-Tissue Expression projects) (http://gepia.cancer-pku.cn) [15]. Survival analysis in GEPIA2 for specific gene in TCGA-CESC dataset was used
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