scholarly journals Guanosine monophosphate synthase upregulation mediates cervical cancer progression by inhibiting the apoptosis of cervical cancer cells via the Stat3/P53 pathway

2021 ◽  
Vol 58 (4) ◽  
Author(s):  
Juan Wang ◽  
Yuhong Wu ◽  
Yan Li ◽  
Yamei Wang ◽  
Fangrong Shen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Guanosine Monophosphate ◽  
P53 Pathway ◽  
Cervical Cancer Cells

scholarly journals RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review

2019 ◽  
Vol 20 (9) ◽  
pp. 2183 ◽  
Author(s):  
Peter A. van Dam ◽  
Yannick Verhoeven ◽  
Julie Jacobs ◽  
An Wouters ◽  
Wiebren Tjalma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Uterine Cervix ◽  
Tumor Necrosis ◽  
Immune Therapy ◽  
Mrna Levels ◽  
Cervical Cancer Cells ◽  
Necrosis Factor

RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of tumor necrosis factor (TNF) receptor associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor called osteoprotegerin (OPG), but also has additional more complex levels of regulation. The existing literature on RANK/RANKL signaling in cervical cancer was reviewed, particularly focusing on the effects on the microenvironment. RANKL and RANK are frequently co-expressed in cervical cancer cells lines and in carcinoma of the uterine cervix. RANKL and OPG expression strongly increases during cervical cancer progression. RANKL is directly secreted by cervical cancer cells, which may be a mechanism they use to create an immune suppressive environment. RANKL induces expression of multiple activating cytokines by dendritic cells. High RANK mRNA levels and high immunohistochemical OPG expression are significantly correlated with high clinical stage, tumor grade, presence of lymph node metastases, and poor overall survival. Inhibition of RANKL signaling has a direct effect on tumor cell proliferation and behavior, but also alters the microenvironment. Abundant circumstantial evidence suggests that RANKL inhibition may (partially) reverse an immunosuppressive status. The use of denosumab, a monoclonal antibody directed to RANKL, as an immunomodulatory strategy is an attractive concept which should be further explored in combination with immune therapy in patients with cervical cancer.

scholarly journals Extracellular Vesicles Long Non-Coding RNA AGAP2-AS1 Contributes to Cervical Cancer Cell Proliferation Through Regulating the miR-3064-5p/SIRT1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Li ◽  
Jing Wang ◽  
Hongli Ma ◽  
Li Gao ◽  
Kunxiang Zhao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cervical Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Cervical Cancer Cells

Cervical cancer is one of the most severe and prevalent female malignancies and a global health issue. The molecular mechanisms underlying cervical cancer development are poorly investigated. As a type of extracellular membrane vesicles, EVs from cancer cells are involved in cancer progression by delivering regulatory factors, such as proteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). In this study, we identified an innovative function of extracellular vesicle (EV) lncRNA AGAP2-AS1 in regulating cervical cancer cell proliferation. The EVs were isolated from the cervical cancer cells and were observed by transmission electron microscopy (TEM) and were confirmed by analyzing exosome markers. The depletion of AGAP2-AS1 by siRNA significantly reduced its expression in the exosomes from cervical cancer and in the cervical cancer treated with AGAP2-AS1-knockdown exosomes. The expression of AGAP2-AS1 was elevated in the clinical cervical cancer tissues compared with the adjacent normal tissues. The depletion of EV AGAP2-AS1 reduced cell viabilities and Edu-positive cervical cancer cells, while it enhanced cervical cancer cell apoptosis. Tumorigenicity analysis in nude mice showed that the silencing of EV AGAP2-AS1 attenuated cervical cancer cell growth in vivo. Regarding the mechanism, we identified that AGAP2-AS1 increased SIRT1 expression by sponging miR-3064-5p in cervical cancer cells. The overexpression of SIRT1 or the inhibition of miR-3064-5p reversed EV AGAP2-AS1 depletion-inhibited cancer cell proliferation in vitro. Consequently, we concluded that EV lncRNA AGAP2-AS1 contributed to cervical cancer cell proliferation through regulating the miR-3064-5p/SIRT1 axis. The clinical values of EV lncRNA AGAP2-AS1 and miR-3064-5p deserve to be explored in cervical cancer diagnosis and treatments.

scholarly journals Abnormal level of paxillin in cervical cancer cells is involved in tumor progression and invasion

2021 ◽  
Author(s):  
Hongqing Gu ◽  
Jing Wen
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Uterine Cervical Cancer ◽  
Cancer Growth ◽  
Over Expression ◽  
Apoptosis Inhibition ◽  
Cervical Cancer Cells ◽  
Elevated Expression ◽  
Abnormal Level

Human papillomavirus (HPV) is the primary causative agent for the uterine cervical cancer. The expression of oncoproteins E6/E7 promotes apoptosis inhibition and increases the risk of cervical cancer progression. Some research reported that elevated expression of paxillin (PXN) stimulated cancer growth and invasion. However, the clinical significance of PXN in cervical cancer has not been well characterized so far. We found that PXN mRNA expression and protein level are significantly upregulated in cervical cancer cells compared to adjacent normal cells. Furthermore, the paxillin over-expression was correlated with potential of tumorigenesis and invasion. Cervical cancer cells with increased paxillin expression had an ability to form more tumor clones and were characterized by higher invasiveness as well. Therefore, our findings suggest that paxillin may act as an important prognostic factor for cervical cancer patients as it promotes tumor regeneration and invasion.

scholarly journals miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2

2017 ◽  
Vol 25 (4) ◽  
pp. 463-470 ◽  
Author(s):  
Changlin Wang ◽  
Bin Zhou ◽  
Min Liu ◽  
Ying Liu ◽  
Rui Gao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Flow Cytometric Analysis ◽  
Luciferase Reporter ◽  
Tumor Tissues ◽  
Incidence And Mortality ◽  
Cervical Cancer Cells ◽  
Cancer Tumor ◽  
Human Cervical Cancer

Cervical cancer is one of the most common cancers in females, with a high incidence and mortality around the world. However, the pathogenesis in cervical cancer is not completely known. In the present study, we investigated the role of miR-126-5p and Bcl2l2 in cervical cancer cells. First, miR-126-5p expression was aberrantly downregulated in human cervical cancer tumor tissues in comparison with normal tissues, as evaluated by RT-PCR. Consistently, the levels of miR-126-5p were also significantly reduced in cervical cancer cell lines when compared to normal cervical epithelial cells. Flow cytometric analysis showed that the rate of apoptosis of cervical cancer cells was significantly increased by miR-126-5p overexpression but inhibited by miR-126-5p inhibitor. A similar change pattern was observed in the expression of apoptosis-regulated protein caspase 3 in cervical cancer cells transfected with miR-126-5p mimic or inhibitor. By bioinformatic prediction with online databases and verification using luciferase reporter assay, we then identified that Bcl2l2 is a direct target of miR-126-5p in cervical cancer cells. The expression of Bcl2l2 was strongly downregulated by the miR-126-5p mimic but upregulated by the miR-126-5p inhibitor in cervical cancer cells, and Bcl2l2 expression was significantly increased in human cervical cancer tumor tissues, which was negatively correlated with miR-126-5p levels. Furthermore, we confirmed that the rate of apoptosis was significantly increased by Bcl2l2 silencing in cervical cancer cells, which was not affected by the miR-126-5p inhibitor. In addition, the increased apoptosis of cells by the miR-126-5p mimic was inhibited by Bcl2l2 overexpression. In summary, miR-126-5p plays an inhibitory role in human cervical cancer progression, regulating the apoptosis of cancer cells via directly targeting Bcl2l2. This might provide a potential therapeutic target for cervical cancer.

scholarly journals Aquaporin-8 is a novel marker for progression of human cervical cancer cells

2021 ◽  
pp. 1-10
Author(s):  
Weibo Li ◽  
Yizuo Song ◽  
Chunyu Pan ◽  
Junhui Yu ◽  
Jianan Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Protein Expression ◽  
Western Blot ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Siha Cells ◽  
Potential Marker ◽  
Cervical Cancer Cells

BACKGROUND: Role of aquaporin-8 (AQP8) in cervical cancer has not been fully elucidated. OBJECTIVE: We aim to explore the impacts of AQP8 on viability, apoptosis and metastasis in cervical cancer cells. METHODS: AQP8 protein expression in cervical carcinoma specimens and cell lines was detected by IHC and western blot analysis. Lentivirus-mediated transfection was used to upregulate and knockdown AQP8 in cells. Cell viability and apoptosis were assessed by CCK-8 and flow cytometry assays, respectively. Transwell experiments were conducted to investigate cell invasive and migratory capabilities. EMT-related markers were detected by western blot analysis. RESULTS: A strong positive of AQP8 protein expression was observed in cervical cancer tissues. Western blot analysis confirmed overexpression and knockdown of AQP8 in SiHa cells. AQP8-overexpressed SiHa cells displayed an enhanced viability, reduced apoptotic rate, increased invasive and migratory abilities. Knockdown of AQP8 inhibited the viability, promoted the apoptosis, and suppressed invasion and migration. Furthermore, AQP8 overexpression significantly upregulated vimentin and N-cadherin, and downregulated E-cadherin, which were reversed by AQP8 knockdown. CONCLUSIONS: AQP8 increases viability, inhibits apoptosis, and facilitates metastasis in SiHa cells. This may be associated with EMT-related markers regulated by AQP8. AQP8 could serves as a potential marker for cervical cancer progression.

scholarly journals The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongling Zou ◽  
Lei Dong ◽  
Chenying Li ◽  
Zhe Yin ◽  
Shuan Rao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cervical Cancer Cell Line ◽  
Translation Efficiency ◽  
Cell Line Hela ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration ◽  
Human Cervical Cancer

Abstract Background Since FTO was recognized as the first m6A demethylase, the understanding of its biological function has been widely expanded. However, the role of FTO in cervical cancer tumorigenesis remains unclear. Methods In this study, we first analyzed the expression of FTO in two independent human cancer datasets and evaluated the correlation between FTO level and cervical cancer progression. Using small hairpin RNA technology, we explored the function of FTO in cervical cancer cell line Hela and SiHa cells, respectively. We then determined the FTO targets by performing transcriptional profile with FTO deficient and competent Hela cells, and finally validated these targets with ribosome profiling and functional rescue experiments. Results Our data suggested that FTO was frequently overexpressed in human cervical cancer tissues and highly correlated with cervical cancer progression. FTO serves as an oncogenic regulator for cervical cancer cells’ proliferation and migration which is vastly depended on its demethylase activity. Mechanistically, FTO interacts with transcripts of E2F1 and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc, however, either overexpress E2F1 or Myc sufficiently compensates the FTO deficiency which decreases cell proliferation and migration. Conclusions Our study indicates that FTO plays important oncogenic role in regulating cervical cancer cells’ proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts. FTO represents a potential drug candidate for cervical cancer therapy.

scholarly journals Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Juliana L. Souza ◽  
Karina Martins-Cardoso ◽  
Isabella S. Guimarães ◽  
Andréia C. de Melo ◽  
Angela H. Lopes ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumor Biology ◽  
Platelet Activating Factor ◽  
The Cancer Genome Atlas ◽  
Strong Positive Correlation ◽  
Poor Overall Survival ◽  
Cervical Cancer Cells

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

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