Interactome analysis of gene expression profiles of cervical cancer reveals dysregulated mitotic gene clusters

摘要

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.