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Interactome analysis of gene expression profiles of cervical cancer reveals dysregulated mitotic gene clusters
Jing Cheng1, Xiaosheng Lu1, Jianguang Wang2
1Reproductive Health Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China.
Abstract:
Cervical cancer is the second most common malignancy in women worldwide. HPV infections are the leading cause of cervical cancer. Although progress has been made in understanding cervical cancer, knowledge of oncogenic gene clusters that participate in squamous-cell mitosis is still lacking. We performed a computational analysis with qRT-PCR validation of gene expression profiles of cervical cancer tissues. Genes involved in muscle contraction and development were downregulated in cervical cancer tissues, suggesting decreased muscle function in cervical cancer. Among the genes that were upregulated in cervical cancer tissues, several groups of genes were found to interact with each other and synergistically participate in multiple stages of mitosis including DNA replication, cell cycle progression, and cell division. An analysis of gene regulatory networks showed that replicative helicase proteins (MCM2, MCM4, MCM5, MCM6, and MCM10) and DNA polymerases (PLOA1/E2/E3/Q) have enhanced DNA replication in cervical cancer. A group of kinases, cyclins, and transcriptional factors were found to promote cell cycle transitions from G1 phase to S phase and from G2 phase to M phase. Those proteins included CDK1, CCNA2, CCNB2, and TFDP2. Moreover, a set of motor proteins (KIF11, KIF14 and KIF4A) and their partner PRC1 were found to mediate cytokinesis during cervical cancer progression. Those findings present a better understanding of the mechanism of mitosis in cervical cancer from an interactomic perspective and provide potential targets for anticancer therapies.
Insights
This study reveals key genes driving cervical cancer cell division (mitosis). Understanding these oncogenic gene clusters offers new targets for anticancer therapies against HPV-related cervical cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer is a major global health concern, primarily caused by HPV infections.
- While progress has been made, the specific oncogenic gene clusters involved in squamous-cell mitosis remain poorly understood.
- Identifying these genes is crucial for developing targeted therapies.
Purpose of the Study:
- To computationally analyze and validate gene expression profiles in cervical cancer tissues.
- To identify and characterize oncogenic gene clusters that regulate mitosis in cervical cancer.
- To explore potential therapeutic targets based on altered gene expression and interactions.
Main Methods:
- Computational analysis of gene expression profiles from cervical cancer tissues.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for validation.
- Gene regulatory network analysis to identify interacting gene clusters and pathways.
Main Results:
- Downregulation of genes associated with muscle contraction and development observed.
- Upregulation of gene clusters synergistically involved in DNA replication, cell cycle progression, and cell division identified.
- Enhanced DNA replication by replicative helicase proteins (MCM family) and DNA polymerases.
- Promotion of cell cycle transitions by kinases, cyclins (CDK1, CCNA2, CCNB2), and transcription factors (TFDP2).
- Mediation of cytokinesis by motor proteins (KIFs) and PRC1.
Conclusions:
- Findings provide a comprehensive interactomic perspective on cervical cancer mitosis.
- Identified gene clusters and proteins represent potential therapeutic targets for cervical cancer treatment.
- This research enhances the understanding of molecular mechanisms underlying cervical cancer progression.
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