Potential biomarkers and therapeutic targets in cervical cancer: Insights from the meta-analysis of transcriptomics data within network biomedicine perspective

Abstract

The malignant neoplasm of the cervix, cervical cancer, has effects on the reproductive tract. Although infection with oncogenic human papillomavirus is essential for cervical cancer development, it alone is insufficient to explain the development of cervical cancer. Therefore, other risk factors such as host genetic factors should be identified, and their importance in cervical cancer induction should be determined. Although gene expression profiling studies in the last decade have made significant molecular findings about cervical cancer, adequate screening and effective treatment strategies have yet to be achieved. In the current study, meta-analysis was performed on cervical cancer-associated transcriptome data and reporter biomolecules were identified at RNA (mRNA, miRNA), protein (receptor, transcription factor, etc.), and metabolite levels by the integration of gene expression profiles with genome-scale biomolecular networks. This approach revealed already-known biomarkers, tumor suppressors and oncogenes in cervical cancer as well as various receptors (e.g. ephrin receptors EPHA4, EPHA5, and EPHB2; endothelin receptors EDNRA and EDNRB; nuclear receptors NCOA3, NR2C1, and NR2C2), miRNAs (e.g., miR-192-5p, miR-193b-3p, and miR-215-5p), transcription factors (particularly E2F4, ETS1, and CUTL1), other proteins (e.g., KAT2B, PARP1, CDK1, GSK3B, WNK1, and CRYAB), and metabolites (particularly, arachidonic acids) as novel biomarker candidates and potential therapeutic targets. The differential expression profiles of all reporter biomolecules were cross-validated in independent RNA-Seq and miRNA-Seq datasets, and the prognostic power of several reporter biomolecules, including KAT2B, PCNA, CD86, miR-192-5p and miR-215-5p was also demonstrated. In this study, we reported valuable data for further experimental and clinical efforts, because the proposed biomolecules have significant potential as systems biomarkers for screening or therapeutic purposes in cervical carcinoma.

Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

“…The power of multi-omics analyses within network biomedicine perspective [14] in elucidation of molecular signatures in human diseases was previously shown in many human diseases such as head and neck cancers [15], esophageal squamous cell carcinoma [16], triple negative breast cancer [17], cervical cancer [18], ovarian cancer [19] and ovarian diseases [20], psoriasis [21] and type 2 diabetes [22]. Therefore, in this study, systems-based approaches have been considered to explore the potential biomarker signatures at protein (i.e., hub proteins and TFs) and RNA levels (i.e., miRNAs and mRNAs) ( Figure 1).…”

The STAT3‐miR‐223‐TGFBR3/HMGCS1 axis modulates the progression of cervical carcinoma

“…Furthermore, in our present work, we identified two novel targets of miR‐223, namely TGFBR3 and HMGCS1. Although few studies have discussed the role of these two proteins in tumorigenesis, these proteins have been found to be downregulated in cervical cancer (Kori and Yalcin Arga, 2018). Similarly, our data indicate that TGFBR3 and HMGCS1 function as repressors of tumorgenesis in CSCC.…”

“…The knockdown of HMGCS1 results in more attenuated cell proliferation rates in BRAF V600D/E ‐expressing melanoma cells (Zhao et al ., 2017). HMGCS1 is expressed at a low level in cervical cancer based on analysis of five independent transcriptomic Gene Expression Omnibus (GEO) datasets suggesting that HMGCS1 may play another role in cancer progression (Kori and Yalcin Arga, 2018).…”

LncRNA HAND2‐AS1 represses cervical cancer progression by interaction with transcription factor E2F4 at the promoter of C16orf74

“…E2F transcription factor family members play crucial roles in the regulation of cell cycle, cell differentiation, DNA repair and cell death 14 . According to a previous study, E2F4 participates in the regulation of transcription of multiple core genes in the tumorigenesis of Burkitt lymphoma 15 and cervical cancer 16 . Chromosome 16 open reading frame 74 (C16orf74), also known as MGC17624, is a gene locus on chromosome 16q24.1, whose function requires further elucidation 17 .…”