Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies

Lin, Min; Ye, Miaomiao; Zhou, Jingyang; Wang, Z. Peter; Zhu, Xueqiong

doi:10.1016/j.csbj.2019.02.001

Cited by 48 publications

(27 citation statements)

References 145 publications

(180 reference statements)

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“…To date, the occurrence and development of CC is hypothesized to be linked with persistent HPV infection (100); however, the specific molecular mechanisms require further investigation. In addition, although a number of studies are examining the molecular mechanisms of CC (101)(102)(103)(104), the detailed pathological process remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive gene and pathway analysis of cervical cancer progression

Fang

et al. 2020

Oncol Lett

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Cervical Cancer is one of the leading causes of cancer-associated mortality in women. The present study aimed to identify key genes and pathways involved in cervical cancer (CC) progression, via a comprehensive bioinformatics analysis. The GSE63514 dataset from the Gene Expression Omnibus database was analyzed for hub genes and cancer progression was divided into four phases (phases I-IV). Pathway enrichment, protein-protein interaction (PPI) and pathway crosstalk analyses were performed, to identify key genes and pathways using a criterion nodal degree ≥5. Gene pathway analysis was determined by mapping the key genes into the key pathways. Co-expression between key genes and their effect on overall survival (OS) time was assessed using The Cancer Genome Atlas database. A total of 3,446 differentially expressed genes with 107 hub genes were identified within the four phases. A total of 14 key genes with 11 key pathways were obtained, following extraction of ≥5 degree nodes from the PPI and pathway crosstalk networks. Gene pathway analysis revealed that CDK1 and CCNB1 regulated the cell cycle and were activated in phase I. Notably, the following terms, 'pathways in cancer', 'focal adhesion' and the 'PI3K-Akt signaling pathway' ranked the highest in phases II-IV. Furthermore, FN1, ITGB1 and MMP9 may be associated with metastasis of tumor cells. STAT1 was indicated to predominantly function at the phase IV via cancer-associated signaling pathways, including 'pathways in cancer' and 'Toll-like receptor signaling pathway'. Survival analysis revealed that high ITGB1 and FN1 expression levels resulted in significantly worse OS. CDK1 and CCNB1 were revealed to regulate proliferation and differentiation through the cell cycle and viral tumorigenesis, while FN1 and ITGB1, which may be developed as novel prognostic factors, were co-expressed to induce metastasis via cancer-associated signaling pathways, including PI3K-Art signaling pathway, and focal adhesion in CC; however, the underlying molecular mechanisms require further research.

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Section: Discussionmentioning

confidence: 99%

Comprehensive gene and pathway analysis of cervical cancer progression

Fang

et al. 2020

Oncol Lett

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“…Cervical cancer is one of the leading causes of death among women worldwide [ 1 ], currently ranking as the fourth most prevalent cause of cancer death [ 2 ]. Cervical cancer is associated with a poor prognosis due to the characteristic invasion and metastasis and thus requires more efficient therapeutic targets for the treatment [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: microRNA-375 released from extracellular vesicles of bone marrow mesenchymal stem cells exerts anti-oncogenic effects against cervical cancer

2020

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Background Cervical cancer is the most prevalent gynecological malignancies accompanied by high mortality, where finding a more effective therapeutic option for cervical cancer is necessary. The inhibitory role of microRNAs (miRNAs) derived from the extracellular vesicles (EVs) of the bone marrow mesenchymal stem cells (BMSCs) was analyzed in cervical cancer. Methods Expression of miR-375 was examined by RT-qPCR in cervical cancer cell lines. The targeting relation between miR-375 and maternal embryonic leucine zipper kinase (MELK) was predicted by bioinformatics analysis and verified by dual-luciferase reporter gene assay. Isolated BMSCs were transfected with lentivirus-mediated vectors, followed by EV extraction. The morphology of EVs was then identified using a NanoSight particle size analyzer and transmission electron microscope (TEM). The biological properties of cervical cancer cells were evaluated using Transwell, EdU, and TUNEL assays, respectively. Xenograft tumors in nude mice were observed to assess cervical tumorigenesis in vivo. Results Low expression of miR-375 and high expression of MELK were detected in cervical cancer samples. MELK was identified as the target gene of miR-375, which was negatively correlated with miR-375 levels. Overexpression of miR-375 suppressed proliferation, migration, and invasion of cervical cancer cells, but enhanced cell apoptosis by cooperating with downregulated MELK expression. miR-375 transferred from BMSC-derived EVs exerted the same effects on cell biological activities. Xenograft assays in vivo proved that miR-375 from BMSC-derived EVs inhibited tumor growth. Conclusion The present study highlighted the role of miR-375 from BMSC-derived EVs in suppressing the progression of cervical cancer, which may contribute to the discovery of novel potential biomarkers for cervical cancer therapy.

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“…Although earlier studies have reported on progress in elucidating the potential molecular mechanism of CC development [ 22 , 23 ], the fundamental knowledge of this mechanism remains problematic. As HPVs are DNA viruses with epithelial tropisms, HPV infection results in activation of the DNA damage repair mechanism [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

Dudea-Simon

Mihu

Irimie

et al. 2020

IJMS

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In spite of being a preventable disease, cervical cancer (CC) remains at high incidence, and it has a significant mortality rate. Although hijacking of the host cellular pathway is fundamental for developing a better understanding of the human papillomavirus (HPV) pathogenesis, a major obstacle is identifying the central molecular targets involved in HPV-driven CC. The aim of this study is to investigate transcriptomic patterns of HPV-infected and normal tissues to identify novel prognostic markers. Analyses of functional enrichment and interaction networks reveal that altered genes are mainly involved in cell cycle, DNA damage, and regulated cell-to-cell signaling. Analysis of The Cancer Genome Atlas (TCGA) data has suggested that patients with unfavorable prognostics are more likely to have DNA repair defects attributed, in most cases, to the presence of HPV. However, further studies are needed to fully unravel the molecular mechanisms of such genes involved in CC.

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Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies

Cited by 48 publications

References 145 publications

Comprehensive gene and pathway analysis of cervical cancer progression

Comprehensive gene and pathway analysis of cervical cancer progression

RETRACTED ARTICLE: microRNA-375 released from extracellular vesicles of bone marrow mesenchymal stem cells exerts anti-oncogenic effects against cervical cancer

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

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