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In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.

ABSTRACT: Cervical cancer (CC) is the fourth most common pathology in women worldwide and presents a high impact in developing countries due to limited financial resources as well as difficulties in monitoring and access to health services. Human papillomavirus (HPV) is the leading cause of CC, and despite the approval of prophylactic vaccines, there is no effective treatment for patients with pre-existing infections or HPV-induced carcinomas. High-risk (HR) HPV E6 and E7 oncoproteins are considered biomarkers in CC progression. Since the E6 structure was resolved, it has been one of the most studied targets to develop novel and specific therapeutics to treat/manage CC. Therefore, several small molecules (plant-derived or synthetic compounds) have been reported as blockers/inhibitors of E6 oncoprotein action, and computational-aided methods have been of high relevance in their discovery and development. In silico approaches have become a powerful tool for reducing the time and cost of the drug development process. Thus, this review will depict small molecules that are already being explored as HR HPV E6 protein blockers and in silico approaches to the design of novel therapeutics for managing CC. Besides, future perspectives in CC therapy will be briefly discussed.

SUBMITTER: Gomes D

PROVIDER: S-EPMC8400112 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.

Gomes Diana D Silvestre Samuel S Duarte Ana Paula AP Venuti Aldo A Soares Christiane P CP Passarinha Luís L Sousa Ângela Â

Pharmaceuticals (Basel, Switzerland) 20210729 8

Cervical cancer (CC) is the fourth most common pathology in women worldwide and presents a high impact in developing countries due to limited financial resources as well as difficulties in monitoring and access to health services. Human papillomavirus (HPV) is the leading cause of CC, and despite the approval of prophylactic vaccines, there is no effective treatment for patients with pre-existing infections or HPV-induced carcinomas. High-risk (HR) HPV E6 and E7 oncoproteins are considered bioma ...[more]

PMID: 34451838

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Project description:BackgroundThe goal of this bioinformatics research is to get a comprehensive understanding of the driver genes and their function in the development, progression, and treatment of cervical cancer. This study constitutes a pioneering attempt, adding to our knowledge of genetic diversity and its ramifications.Material and methodsIn this project, we use bioinformatics and systems biology methods to identify candidate transcription factors and the genes they regulate in order to identify microRNAs and LncRNAs that regulate these transcription factors and lead to the discovery of new medicines for the treatment of cervical cancer. From the differentially expressed genes available via GEO's GSE63514 accession, we use driver genes to choose these candidates. We then used the WGCNA tool in R to rebuild the co-expression network and its modules. The hub genes of each module were determined using CytoHubba, a Cystoscope plugin. The biomarker potential of hub genes was analyzed using the UCSC Xena browser and the GraphPad prism program. The TRRUST database is used to locate the TFs that regulate the expression of these genes. In order to learn how drugs, MicroRNAs, and LncRNAs interact with transcription factors, we consulted the Drug Target Information Database (DGIDB), the miRWalk database, and the LncHub database. Finally, the online database Enrichr is utilized to analyze the enrichment of Gene Ontology and KEGG pathways.ResultsBy combining the mRNA expression levels of 2041 driver genes from 14 early-stage Cervical cancer and 24 control samples, a co-expression network was built. The cluster analysis shows that the collection of shared genes may be broken down into seven distinct groups, or "modules." According to the average linkage hierarchical clustering and Summary smaller than 2, we found five modules (represented by the colors blue, brown, red, green, and grey) in our research. Then, we identify 5 high-degree genes from these modules that may serve as diagnostic biomarkers (ZBBX, PLCH1, TTC7B, DNAH7, and ZMYND10). In addition, we identify four transcription factors (SRF, RELA, NFKB1, and SP1) that regulate the expression of genes in the co-expression module. Drugs, microRNAs, and long noncoding RNAs are then shown to cooperate with transcription factors. At last, the KEGG database's pathways were mined for information on how the co-expression module fits within them. More clinical trials are required for more trustworthy outcomes, and we collected this data using bioinformatics methods.ConclusionThe major goal of this research was to identify diagnostic and therapeutic targets for cervical cancer by learning more about the involvement of driver genes in cancer's earliest stages.

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In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.

Publications

In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.

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