Angiogenesis In Cervical Cancer Research Articles

Retraction: "Downregulation of microRNA-205 inhibits cell invasion and angiogenesis of cervical cancer through TSLC1-mediated Akt signaling pathway".

Retraction: "Downregulation of microRNA-205 inhibits cell invasion and angiogenesis of cervical cancer through TSLC1-mediated Akt signaling pathway" by Fang Zhang, Jian Liu, Bei-Bei Xie, J Cell Physiol 2019, 234: 18626-18638. The above article, published online on 2 May 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcp.28501) has been retracted by agreement between the authors, the journal's Editors in Chief, Alexander Hutchison, and Wiley Periodicals LLC. The retraction has been agreed due to concerns related to the data presented in the article. Several flaws and inconsistencies between results presented and experimental methods described were found. Additionally, some figure elements have been published elsewhere in a different scientific context. Thus, the conclusions of this article are considered to be invalid by the editors.

Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth

ABSTRACT Background The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer. Research design and methods Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation. Results In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice. Conclusions We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.

Ultrasound Microvessel Visualization in Cervical Cancer: Association Between Novel Ultrasound Techniques and Histologic Microvessel Densities.

The aim of the work described here was to evaluate the feasibility of superb microvascular imaging (SMI) and vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubble (MBVEGFR2)-based ultrasound molecular imaging (USMI) for visualizing microvessels in cervical cancer. Hela cells were used to establish subcutaneous cervical cancer models. SMI and MBVEGFR2-based USMI were performed, and the results were compared with intratumoral microvessel density (MVD) in four groups based on tumor diameter (<3 mm, 3-5 mm, 5-7 mm and ≥7 mm). The vascularization index (VI, %) was evaluated for SMI, and the normalized intensity difference (NID) for USMI. Tumors with diameters ranging from 3 to 5 mm had the highest VI (39.07 ± 1.58) in SMI, and VI significantly decreased with increasing tumor size (all p values <0.001). The strongest signal intensity was observed in very early tumors (d < 3 mm: 43.80 ± 3.58%) after MBVEGFR2 administration; the NID gradually decreased with increasing diameter of tumors (all p values=0.007). However, no significant differences were observed in NID after administration of non-targeted (control) microbubbles (MBCon) (all p values=0.125). MBVEGFR2-based USMI had the strongest correlation with MVD in displaying microvessels of cervical cancer compared with SMI and MBCon (R2=0.78 vs. R2=0.40 and R2=0.38). These findings validate the superiority and accuracy of MBVEGFR2-based USMI for microvessel imaging and monitoring of angiogenesis in cervical cancer compared with SMI and MBCon. Nonetheless, SMI remains an alternative to microvessel imaging when ultrasonic contrast agent use is contraindicated.

Mechanism of Paris polyphylla saponin II inducing autophagic to inhibit angiogenesis of cervical cancer.

Paris polyphylla saponin II (PPII) has good biological activity in inhibiting tumor angiogenesis. However, the mechanism of its action is still unclear. This study first observed the inhibitory effect of PPII on cervical cancer cells (Hela) through the establishment of MTT and nude mouse subcutaneous transplantation tumor models. Afterwards, then, we collected Hela cell supernatant for culturing HUVEC cells and treated it with PPII. Observe the invasion, migration, and lumen formation ability of drugs through Transwell, cell scratch test, and angiogenesis experiment. MDC staining was used to observe positive staining in the perinuclear area, AO staining was used to observe acidic areas, and transmission electron microscopy staining was used to observe ultrastructure and autophagy. In addition, the effects of PPII on autophagy- and angiogenesis-related protein expression were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction. Finally, HUVECs were treated with autophagy inhibitors 3-MA, CQ, and PI3K inhibitor LY294002, respectively. The results showed that the autophagy level of cells treated with PPII was significantly increased. In addition, adding autophagy inhibitors can effectively inhibit angiogenesis in cervical cancer. Further research suggests that PPII induces autophagy in HUVEC cells by regulating the PI3K/AKT/mTOR signaling pathway, thereby affecting angiogenesis and inhibiting Hela cell proliferation, lumen formation, invasion, and migration.

Exploring the prognostic significance of PKCε variants in cervical cancer

BackgroundProtein Kinase C-epsilon (PKCε) is a member of the novel subfamily of PKCs (nPKCs) that plays a role in cancer development. Studies have revealed that its elevated expression levels are associated with cervical cancer. Previously, we identified pathogenic variations in its different domains through various bioinformatics tools and molecular dynamic simulation. In the present study, the aim was to find the association of its variants rs1553369874 and rs1345511001 with cervical cancer and to determine the influence of these variants on the protein-protein interactions of PKCε, which can lead towards cancer development and poor survival rates.MethodsThe association of the variants with cervical cancer and its clinicopathological features was determined through genotyping analysis. Odds ratio and relative risk along with Fisher exact test were calculated to evaluate variants significance and disease risk. Protein-protein docking was performed and docked complexes were subjected to molecular dynamics simulation to gauge the variants impact on PKCε’s molecular interactions.ResultsThis study revealed that genetic variants rs1553369874 and rs1345511001 were associated with cervical cancer. Smad3 interacts with PKCε and this interaction promotes cervical cancer angiogenesis; therefore, Smad3 was selected for protein-protein docking. The analysis revealed PKCε variants promoted aberrant interactions with Smad3 that might lead to the activation of oncogenic pathways. The data obtained from this study suggested the prognostic significance of PRKCE gene variants rs1553369874 and rs1345511001.ConclusionThrough further in vitro and in vivo validation, these variants can be used at the clinical level as novel prognostic markers and therapeutic targets against cervical cancer.

In vivo real-time monitoring of the development of hypoxia and angiogenesis in cervical cancer

The growth of solid tumors is inevitably accompanied by hypoxia and angiogenesis. Understanding the true state of tissue hypoxia and angiogenesis during tumor progression will help further comprehend the tumor microenvironment and cancer therapy. Here, we provided a novel strategy for the long-term tracking of tumor hypoxia and angiogenesis in cervical cancer. The hypoxia response elements (HRE)-driven luciferase (LUC) reporter gene transfected cervical cancer cell lines were constructed for hypoxia visualization. The hypoxia response activity of HRE-driven LUC was verified in HeLa cells and then monitored via the HeLa-HRE-LUC tumor-bearing mouse models by bioluminescence imaging (BLI). An oxygen-sensitive nanoparticle was constructed for glycerol monooleate cubic liquid crystal material loaded with Ir(piq)3/IR780 and could be used for phosphorescence-fluorescence imaging. The imaging result showed that the nanoparticles labeled the low oxygen region overlapped with the BLI signal region detected by HRE-driven LUC in vivo, which confirmed that the hypoxia visualization platform could genuinely reflect the hypoxia level in vivo. The angiogenesis in vivo was reflected by changes in deoxygenated/oxygenated hemoglobin detected by photoacoustic imaging. Besides these, anticancer drug apigenin down-regulated HIF-1α and VEGF under hypoxia conditions and inhibited the tube formation in vitro. Then, the inhibition effects were verified in the hypoxia and angiogenesis visualization model in vivo. This study confirmed a novel in vivo real-time monitoring of tumor hypoxia and angiogenesis strategy, which can provide useful information for further research on cancer progression and anticancer therapy.

YTHDC1 inhibits cell proliferation and angiogenesis in cervical cancer by regulating m6A modification of SOCS4 mRNA

YTHDC1 inhibits cell proliferation and angiogenesis in cervical cancer by regulating m6A modification of SOCS4 mRNA

ITGA5 promotes tumor angiogenesis in cervical cancer.

Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5-associated differentially expressed genes. Analyses of single-cell RNA-seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT-PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5-associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5-targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K-Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p-AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1-targeting siRNA showed fibronectin may play a critical role on ITGA5-mediated angiogenesis. ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer.

Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression.

Evidence has indicated that lysine methyltransferase 2B (KMT2B), a major H3K4 tri-methyltransferase (H3K4me3), contributes to the development of various cancers; however, its role in cervical cancer (CC) is unclear. In this study, increased KMT2B expression was observed in human CC specimens and significantly associated with poor prognosis. The condition medium of KMT2B-overexpressing cells facilitated angiogenesis in vitro. In the subcutaneous model of human CC, KMT2B overexpression significantly promoted tumor growth and increased tumor vascular density. Meanwhile, KMT2B enhanced the migration and invasion of CC cells and promoted their metastasis to bone in a tail-vein-metastasis model. Mechanistically, the genes upregulated by KMT2B were significantly enriched in PI3K-AKT pathway. Using H3K4me3 ChIP-seq analysis, we found increased H3K4me3 level at EGF promoter region in KMT2B-overexpressing HeLa cells. ChIP-qPCR experiments not only confirmed the increased H3K4me3 level of EGF promoter but also determined that in KMT2B-overexpressing HeLa cells, KMT2B increased binding with the EGF promoter. Blocking EGFR diminished the KMT2B-induced PI3K-AKT signaling activation and CC cell migration and invasion. Moreover, EGFR inhibitors abolished the KMT2B-drived tube formation capacity of HUVECs. In conclusion, KMT2B facilitates CC metastasis and angiogenesis by upregulating EGF expression, and may serve as a new therapeutic target for CC.

TIE2-high cervical cancer cells promote tumor angiogenesis by upregulating TIE2 and VEGFR2 in endothelial cells

Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (TIE2), the receptor for angiopoietins, has been found highly expressed in cervical cancer and associated with poor prognosis. However, the potential role of tumoral TIE2 in cervical cancer angiogenesis and the underlying mechanisms remain unexplored. Here, based on multicolor immunofluorescence of 64 cervical cancer tissues, we found that TIE2 level in cervical cancer cells was positively related to shorter survival and higher microvessel density in tumor. In vitro and in vivo experiments verified that TIE2-high cervical cancer cells could promote tumor angiogenesis. TIE2-high tumor cells induced an amplified expression of TIE2 and vascular endothelial growth factor receptor 2(VEGFR2) in HUVECs to promote angiogenesis via TIE2 -AKT/MAPK signals, which could be reversed or partially reversed by TIE2, AKT or MAPK inhibitors and activated by angiopoietin-1 and angiopoietin-2. In conclusion, TIE2-high cervical cancer cells promote tumor angiogenesis by upregulating TIE2 and VEGFR2 in endothelial cells via TIE2-AKT/MAPK axis inside tumor cells.

Endostar Synergizes with Radiotherapy to Inhibit Angiogenesis of Cervical Cancer in a Subcutaneous Xenograft Mouse Model.

To investigate the synergic effect and underlying mechanism of Endostar, a recombinant human endostatin used for anti-angiogenesis, in radiotherapy for cervical cancer. The Cell Counting Kit-8 (CCK-8) assay and plate cloning experiment were first employed to analyze the proliferation of HeLa and SiHa cervical cancer cells and human umbilical vein vascular endothelial cells (HUVECs). Flow cytometry was used to detect apoptosis and cell cycle progression. A tube formation assay was used to assess angiogenesis in vitro. The expression of gamma H2A histone family member X (γ-H2AX) and activation of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were detected by immunofluorescence and western blotting, respectively. In a HeLa xenograft model, tumor tissue expression of CD31 and alpha smooth muscle actin and serum expression of VEGF-A were detected by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay, respectively. The CCK-8 and plate cloning assays showed that Endostar and radiotherapy synergistically inhibited the growth of HUVECs but not HeLa and SiHa cells. The flow cytometric results showed that Endostar only promoted radiotherapy-induced apoptosis and G2/M phase arrest in HUVECs (p < 0.05). Endostar combined with radiotherapy also significantly inhibited tube formation by HUVECs (p < 0.05). Furthermore, Endostar inhibited the radiotherapy-induced expression of γH2AX (p < 0.05) and phosphorylation of VEGFR2/PI3K/AKT/DNA-PK in HUVECs (p < 0.05). IHC showed that Endostar enhanced the inhibitory effect of radiotherapy on the microvessel density in xenograft tumor tissues (p < 0.05), as well as serum VEGF-A expression (p < 0.05). The tumor volume in the combination therapy groups (1200 mm3) was significantly lower than in the control group (2500 mm3; p < 0.05). Our findings provide experimental evidence and a theoretical basis for the application of Endostar in combination with irradiation for anti-cervical cancer treatment.

Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development.

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous women's health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

7-Difluoromethyl-5,4’-dimethoxygenistein inhibited the angiogenesis induced by cervical cancer SiHa cells via inhibiting TLR4/VEGF-A axis (217)

<b>Objectives:</b> VEGF inhibitors, such as bevacizumab, inhibit angiogenesis and improve the prognosis of patients with recurrent or metastatic cervical cancer. Antiangiogenic drugs reduce the formation of immature and poorly functional blood vessels and induce the normalization of blood vessels. However, in many cases, features of the vascular normalization brought by VEGF inhibitors are quickly replaced by marked vascular regression, which in turn will exacerbate the degree of hypoxia in the tumor microenvironment. In addition, a variety of adverse effects of antiangiogenic drugs have also been found at present. Therefore, it is a very attractive work to extract natural molecules that are non-toxic or low in toxicity from plants as antiangiogenic drugs. 7-Difluoromethyl-5,4'-dimethoxygenistein (DFMG) is a new chemical entity synthesized from the genistein extracted from the natural plant fruit soybean by ourselves. Previously, DFMG has been found to maintain plaque stability in atherosclerosis through antiangiogenesis. This study explored the effect of DFMG on angiogenesis in cervical cancer and its possible mechanism. <b>Methods:</b> Cell proliferation was detected by the CCK-8 experiment. The expressions of TLR4 and VEGF-A were detected by Q-PCR and Western blot. Angiogenesis was detected by tubule formation test and chorioallantoic membrane (CAM) test. TLR4 was overexpressed and silenced on SiHa cells to detect its effect on VEGF-A secretion and angiogenesis. The effects of DFMG on VEGF-A secretion and angiogenesis were detected on TLR4-overexpressed or -silenced SiHa cells. <b>Results:</b> 1) 50 μM DFMG can inhibit the activity of Siha cells, but not HUVE-12 cells. 2) DFMG inhibits the formation of tubules induced by Siha cells, while bevacizumab can inhibit the ability of HUVE-12 cells to form tubules, but DFMG and genistein have no effect on it. 3) DFMG inhibits the expression and secretion of VEGF-A protein in Siha cells. 4) Overexpression of TLR4 in Siha cells can antagonize the angiogenesis-inhibiting effect caused by bevacizumab, and the silent expression of TLR4 can antagonize the angiogenesis-promoting effect caused by VEGF-A. 5) The numbers of tubules in the tubule formation experiment and new blood vessels in CAM in the DFMG-treated Siha cells with TLR4 overexpression was significantly higher than that in the DFMG-treated Siha cells with TLR4 silence. 6) The overexpression of TLR4 could antagonize the effect of DFMG on the secretion and expression of VEGF-A in SiHa cells, while the silent expression of TLR4 could cooperate with DFMG to inhibit the secretion and expression of VEGF-A.Fig. 1 <b>Conclusions:</b> DFMG inhibits the angiogenesis induced by cervical cancer Siha cells which could be regulated by TLR4/VEGF-A signaling pathway. DFMG reduces angiogenesis by inhibiting VEGF-A secretion of SiHa cells, which is not observed in normal cells.

EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.

BackgroundCircular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear. MethodsCircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR.Resultscirc_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions.ConclusionsAs a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13046-022-02368-4.

Tumor cell-derived exosomes deliver TIE2 protein to macrophages to promote angiogenesis in cervical cancer.

Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (TIE2)-expressing macrophages (TEMs) are an angiogenesis-promoting subset of tumor-associated macrophages that have been demonstrated to be increased in solid tumors and associated with the progression of cervical cancer. However, the induction mechanism of TEMs remains unclear. Here, based on multicolor immunofluorescence of 58 cervical cancer tissues and the GEPIA database, we found that TEMs were increased in TIE2-high cervical cancer and related to shorter survival. In vitro and in vivo experiments verified that exosomes derived from TIE2-high cervical cancer cells transferred TIE2 protein directly to macrophages, thereby inducing TEMs. Similar to primary TEMs, TEMs induced by tumor-derived exosomes promoted angiogenesis, could be induced by angiopoietin-2, and possessed an M2-like phenotype. In conclusion, exosomes derived from TIE2-high cervical cancer cells induce TEMs by directly transporting TIE2 to promote tumor angiogenesis.

Angiopoietin-like 3 (ANGPTL3) drives cell proliferation, migration and angiogenesis in cervical cancer via binding to integrin alpha v beta 3

ABSTRACT Angiopoietin-like 3 (ANGPTL3) has been uncovered to play an oncogenic role in several kinds of human malignancies. Nevertheless, whether ANGPTL3 functions in cervical cancer (CC) has not yet been reported. This paper is intended to explore the impact of ANGPTL3 on CC cells and elucidate the potential mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to analyze the ANGPTL3 expression. Western blot was also performed to examine integrin αvβ3 protein level. Cell proliferation was evaluated by MTT assay, EdU staining and Western blot analysis. In addition, the migratory and invasive abilities of cells were, respectively, estimated by wound healing and transwell assays. Tube formation assay was performed to determine endothelial cell angiogenesis. Levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) were measured by ELISA. As a result, ANGPTL3 expression was significantly higher in CC cells relative to that in normal cervical cells. Silencing of ANGPTL3 suppressed cell proliferation, migration and invasion. Besides, downregulation of ANGPTL3 inhibited human umbilical vein endothelial cell (HUVEC) angiogenesis and repressed protein level of integrin alpha v beta 3 (αvβ3). Upregulation of αvβ3 offsets the inhibitory effect of ANGPTL3 on proliferation, migration and invasion in CC cells. Upregulated expression of αvβ3 promoted blood vessel formation and secretions of VEGF and VEGFR2. In conclusion, ANGPTL3 silencing may serve as a tumor suppressor in CC through integrin αvβ3, which provides a potentially novel therapeutic target for patients with CC.

Vitexin exerts anti-tumor and anti-angiogensis effects on cervical cancer through VEGFA/VEGFR2 pathway

Vitexin is widely known as a bioactive flavonoid compound, and exerts analgesic and anti-oxidative properties. Antitumor effect of vitexin was identified in various tumors. Role and related mechanism of vitexin in cervical cancer were investigated. Cervical cancer cells were treated with vitexin, and treatment with vitexin reduced cell viability, and decreased number of colonies in cervical cancer. Moreover, cell migration and invasion were repressed by vitexin, and vitexin inhibited angiogenesis of cervical cancer. Vitexin reduced protein expression of Vascular Endothelial Growth Factor A (VEGFA) and Vascular endothelial growth factor receptor 2 (VEGFR2) of cervical cancer in a dosage dependent way. In conclusion, vitexin reduced cell proliferation, migration, invasion and angiogenesis of cervical cancer through inhibition of VEGFA/VEGFR2 signaling.

Long non-coding RNA DUXAP8 elevates RCN2 expression and facilitates cell malignant behaviors and angiogenesis in cervical cancer via sponging miR-1297

BackgroundCervical cancer (CC) endangers women’s health in the world range. Accumulating studies have revealed the crucial regulatory role of long non-coding RNAs (lncRNAs) in multiple malignancies, including CC. Our study aimed to explore the role of lncRNA double homeobox A pseudogene 8 (DUXAP8) in cervical carcinogenesis.MethodsGene expressions in CC were assessed by RT-qPCR. Function experiments and tube formation assays were performed to evaluate the role of DUXAP8 in CC cells. Subcellular fractionation and FISH assays were conducted to determine the subcellular location of DUXAP8. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the mechanism of DUXAP8.ResultsDUXAP8 was notably upregulated in CC cells. Downregulation of DUXAP8 repressed cell malignant behaviors and angiogenesis in CC. Mechanically, DUXAP8 boosted the expression of reticulocalbin-2 (RCN2) through relieving the binding of miR-1297 to RCN2 3’-UTR. Moreover, miR-1297 inhibition and RCN2 overexpression could counteract the inhibitory effects of DUXAP8 knockdown on the malignant phenotypes of CC cells. Besides, enhanced RCN2 expression restored the tumor growth in vivo that was inhibited by DUXAP8 repression.ConclusionsDUXAP8 promotes malignant behaviors in CC cells via regulating miR-1297/RCN2 axis.Graphical

Study on Signal Transduction Pathway of Migration Inhibitory Factor in Angiogenesis of Cervical Cancer

Cervical cancer is a common female malignancy worldwide that accounts for the second in women malignant tumor. Macrophage migration inhibitory factor (MIF) is an important tumor promoter that plays an important role in tumor invasion and metastasis. This study explored MIF and PD98059’s effect on cervical cancer Siha cells to analyze MIF impact on VEGF expression, so as to discuss whether MIF may influence cervical cancer angiogenesis through ERK/MAPK signaling pathway. MIF and PD98059 were adopted to treat Siha cells. Western blot were done to measure MIF, ERK1, and VEGF expression. MTT was applied to determine cell proliferation. ERK1 and VEGF were positively expressed in cells. Cell proliferation was elevated gradually at 24, 48, and 72 h in MIF group and declined in PD98059 group (P &lt; 0.05). ERK1 and VEGF protein significantly elevated after treated by MIF for 48 hours and reduced after intervened by PD98059 for 48 h (P &lt;0.05). ERK1 and VEGF obviously downregulated in both MIF and PD98059 treatment groups without difference between two groups (P &lt;0.05). MIF, ERK1, and VEGF is expressed in cervical cancer SiHa cells. MIF promotes cell proliferation through regulating ERK/MAPK signaling pathway to upregulate ERK1 and VEGF expression.

Bone Marrow Mesenchymal Stem Cell (BMSC) Exosomes Inhibit Angiogenesis and Enhance Autophagy Through Decreasing miR-21 in Cervical Cancer

We aimed to explore the mechanism underlying the role of miR-21 derived from bone marrow mesenchymal stem cell exosomes (BMSC-exos) in cervical cancer (CC) and the relation between angiogenesis and autophagy. In this study, BMSC-exos were co-cultured with CC stem cells followed by analysis of miR-21 expression by RT-qPCR, autophagy after hunger-induced feeding by Acridine Orange fluorescent staining, angiogenesis by tube formation assay. Co-culture of BMSC-exos effectively reduced miR-21 expression in CC stem cells and enhanced autophagy as demonstrated by upregulated Beclin1 and LC3B with assembly of autophagosome (p &lt; 0.05), but the autophagy restored later. Moreover, in the presence of BMSC-exos, CC stem cell angiogenesis was suppressed by 79%. In conclusion, BMSC-exos enhance autophagy and inhibit angiogenesis in CC through decreasing miR-21, which provides a novel insight into etiology of CC.