Upregulation of A-kinase-interacting protein 1 (AKIP1) has been observed in breast and esophageal cancers, indicating that AKIP1 may be a potent oncogenic protein. However, the role of AKIP1 in cervical cancer still remains unknown. This study aimed to explore the role of AKIP1 in cervical cancer and to investigate the underlying mechanism of AKIP1 in tumor growth. Expression of AKIP1 in cervical cancer cells was determined by qRT-PCR and western blotting. Cell-Light EdU and colony formation assays were used to determine cell proliferation. CXCL1 and CXCL8 proteins were quantified by ELISA kits. Western blotting and qRT-PCR were used to examine the alterations in signaling-related proteins and mRNA, respectively. Endothelial cell tube formation assay was performed to evaluate the effect of AKIP1 on angiogenesis. A BALB/c nude mouse xenograft model was used to evaluate the role of AKIP1 in vivo. Cancer cell proliferation was inhibited and tumor growth and angiogenesis restrained in BALB/c nude mice by suppressing AKIP1 expression in cervical cancer cell lines. In addition, overexpression of AKIP1 in cervical cancer cells elevated the levels of CXCL1, CXCL2, and CXCL8. These three chemokines were not only involved in endothelial tube formation by binding to the endothelial receptor CXCR2, but also in cervical cancer cell proliferation and clone formation, which were induced by overexpression of AKIP1. Furthermore, we found that AKIP1-induced chemokine expression was decreased by an inhibitor of nuclear factor kappa-B kinase subunit β. These results show that AKIP1 is crucial in cervical cancer angiogenesis and growth by elevating the levels of the NF-κB-dependent chemokines CXCL1, CXCL2, and CXCL8.
MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including cell proliferation, apoptosis, and cell cycle arrest. In this study, we aimed to investigate the biological role of miR-155 in cervical cancer and the underlying molecular mechanism involved in tumorigenesis. The expression of miR-155 in human cervical cancer tissues was detected by real-time PCR. MTT assay and BrdU incorporation assay were used to measure the proliferation of cervical cancer cells. Apoptosis cells and cell cycle distribution were analyzed by flow cytometry. We found that the expression of miR-155 was upregulated in cervical cancer tissues compared to the adjacent non-cancer tissues. Overexpression of miR-155 promoted the proliferation of Hela and SiHa cells. By contrast, downregulation of miR-155 inhibited the growth of cervical cancer cells. Flow cytometry analysis showed that low expression of miR-155 promoted apoptosis and induced cell cycle arrest in Hela and SiHa cells. Moreover, the mRNA and protein expression of LKB1 was significantly reduced in cervical cancer tissues. Luciferase reporter assay demonstrated that LKB1 was a target gene of miR-155, suggesting that miRNA-155 promoted the proliferation of cervical cancer cells by regulating LKB1 expression.
Focal adhesion, regulation of actin cytoskeleton, MAPK and TGFB/SMAD signaling pathway may be important molecular mechanism underlying the pathogenesis of endometriosis.
BackgroundThe aim of this study is to find the potential miRNA expression signature capable of predicting survival time for cervical squamous cell carcinoma (CSCC) patients.MethodsThe expression of 332 miRNAs was measured in 131 (Training cohort) and 130 (Validation cohort) patients with CSCC in the Cancer Genome Atlas (TCGA) data portal. The miRNA expression signature was identified by Cox Proportion Hazard regression model to the Training data set, and subsequently validated in an independent Validation set. Kaplan-Meier curves and the receiver operating characteristic analyses of 5 years were used to access the overall survival of miRNA signature. MiRNA signature-gene target analysis was performed, followed by the construction of the regulatory network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to explore the function of target genes of miRNA signature.ResultsA 2-miRNA expression signature of hsa-mir-642a and hsa-mir-378c associated with survivability was identified in CSCC. Both of them had a significant diagnostic and prognostic value of patients with CSCC. A total of 345 miRNA signature-target pairs were obtained in the miRNA signature-gene target regulatory network, in which 316 genes were targets of has-mir-378c and has-mir-642a. Functional analysis of target genes showed that MAPK signaling pathway, VEGF signaling pathway and endocytosis were the significantly enriched signal pathways that covered most genes.ConclusionsThe 2-miRNA signature adds to the prognostic value of CSCC. In-depth interrogation of the 2-miRNAs will provide important biological insights that finding and developing novel molecularly prediction to improve prognosis for CSCC patients.
Smad ubiquitination regulatory factors (Smurfs) belong to the Nedd4 subfamily of HECT-type E3 ubiquitin ligases. Under normal situations, Smurfs are exactly managed by upstream regulators, and thereby strictly control tumor biological processes, including cell growth, differentiation, apoptosis, polarization, epithelial mesenchymal transition (EMT), and invasion. Disruption of Smurf activity has been implicated in cancer progression, and Smurf activity is controlled by a series of posttranslational modifications (PTMs), including phosphorylation, ubiquitination, neddylation, sumoylation, and methylation. The effect and function of Smurfs depend on PTMs and regulate biological processes. Specifically, these modifications regulate the functional expression of Smurfs by affecting protein degradation and protein interactions. In this review, we summarize the complexity and diversity of Smurf PTMs from biochemical and biological perspectives and highlight the understanding of their roles in cancer.
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