Proliferation Of Cervical Carcinoma Cells Research Articles

The cadherin protein CDH19 mediates cervical carcinoma progression by regulating AKT/NF-κB signaling.

The cell adhesion protein cadherin 19 (CDH19) has been reported to be involved in various types of cancer, but its role in cervical carcinoma remains unknown. We collected and analyzed the patients' data using the GEPIA Kaplan-Meier plotter databases. CDH19 was overexpressed in cervical carcinoma cells to assess its effect on cell proliferation and activation of AKT and NF-κB signaling pathways. A xenograft mouse model was established to study the function of CDH19 in vivo. We found that CDH19 expression was significantly downregulated in cervical carcinoma tissues compared to adjacent normal tissues. Patients with high expression of CDH19 had a significantly better overall survival rate than those with low CDH19 expression. CDH19 expression was negatively correlated with the expression of the proliferation marker Ki-67, and overexpression of CDH19 significantly inhibited cervical carcinoma cell proliferation. Furthermore, overexpression of CDH19 suppressed the activation of the AKT and NF-κB signaling pathways, and CDH19-overexpressing cervical carcinoma tumors exhibited significantly slower growth in vivo. CDH19 plays an important role in cervical carcinoma by suppressing both cell proliferation and the activation of AKT and NF-κB signaling pathways. Therefore, CDH19 may be a potential therapeutic target for cervical carcinoma.

Circ_0002762 Regulates Oncoprotein YBX1 in Cervical Cancer via mir-375 to Regulate the Malignancy of Cancer Cells.

Cervical carcinoma (CC) is the third most common cancer among females and the fourth leading cause of cancer-related death, which poses a serious threat to women's health. This study investigated the biological function and mechanism of circRNA circ_0002762 in the malignant progression of CC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_0002762, microRNA-375 (miR-375) and Y-box binding protein 1 (YBX1) mRNA expressions in CC tissues and cell lines. After circ_0002762 was overexpressed in CC cell lines, cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assays were executed to probe cell growth and migration. Additionally, the targeting relationships between miR-375 and circ_0002762 or YBX1 3'-UTR were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was adopted to examine YBX1 protein levels in CC cells. Circ_0002762 expression was raised in CC tissues and cell lines, and highly expressed circ_0002762 was associated with larger tumor size and lymph node metastasis of CC patients. Circ_0007262 overexpression markedly accelerated the proliferation and migration of CC cells. Besides, miR-375 was revealed to be a downstream target of circ_0002762, and miR-375 overexpression counteracted the promoting effects of circ_0002762 overexpression on CC cell viability and migration. YBX1 was identified as a target of miR-375, and circ_0002762 positively modulated YBX1 expressions through adsorbing miR-375. Circ_0002762 promotes the progression of CC via sponging miR-375 and up-regulating YXB1 expression.

Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway.

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.

Analysis of the Role and Mechanism of ZEB1 in Regulating Cervical Carcinoma Progression via Modulating PD-1/PD-L1 Checkpoint.

Background Cervical carcinoma (CC) is a common and highly malignant tumor in women. The involvement of zinc finger E-box binding homeobox 1 (ZEB1) in many kinds of tumors has been well-documented; however, its role and mechanism in CC remain to be clarified. Objective This study investigated the mechanism of ZEB1 in modulating the growth and metastasis of CC cells. Methods The expression of ZEB1 in CC tissues and adjacent normal counterparts was determined by reverse transcription-polymerase chain reaction (RT-PCR). The correlation between ZEB1 and patient clinicopathological indexes was analyzed. In vitro, gain and loss functions of ZEB1 were performed in C-33A and HeLa cell lines. The proliferation, migration, and invasion of CC cells were detected by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The expression levels of apoptosis-related proteins such as BCL2-associated X (Bax), B-cell lymphoma-2 (Bcl2), and Caspase-3, as well as epithelial-mesenchymal transition (EMT)-associated proteins including E-cadherin, Vimentin, and Snail, were measured by Western blotting. In addition, the targeting relationship between ZEB1 and programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) was predicted by bioinformatics and further verified by dual-luciferase reporter assay. Results ZEB1 was significantly up-regulated in CC tissues compared with normal counterparts. ZEB1 overexpression promoted the migration, proliferation, and invasion of CC cells and inhibited apoptosis, while knocking down ZEB1 contributed to the opposite effects. In addition, experiments on related mechanisms confirmed that ZEB1 targeted the 3'EUTR terminal of PD-1/PD-L1 and negatively regulated its expression. And an interaction between ZEB1 and PD-1/PD-L1 was identified. Conclusion ZEB1 can promote the proliferation and metastasis of CC cells via modulating the PD-1/PD-L1 checkpoint.

DSCAM-AS1 promotes cervical carcinoma cell proliferation and invasion via sponging miR-338-3p.

Deregulated lncRNA DSCAM-AS1 expression was found in several tumors. However, mechanism and functional role of DSCAM-AS1 in cervical carcinoma remain unknown. DSCAM-AS1 was detected in cervical carcinoma specimens and cells by RT-qPCR. CCK-8, Matrigel transwell, and flow cytometry were conducted to determine cell functions. In this research, we firstly we explored DSCAM-AS1 expression in cervical carcinoma cells and specimens. We revealed that DSCAM-AS1 was upregulated in cervical carcinoma lines (C4-1, Caski, Hela, and Siha) compared to GH329 cells. DSCAM-AS1 was upregulated in cervical carcinoma specimens compared to control no-tumor specimens. Overexpression of DSCAM-AS1 induced cervical carcinoma cell growth and cycle. Moreover, our data revealed that miR-338-3p expression was downregulated in cervical carcinoma cells and specimens. There was a negative correlation between miR-338-3p expression and DSCAM-AS1 expression in cervical carcinoma specimens. Elevated expression of miR-338-3p decreased cervical carcinoma cell growth and cycle and invasion. Furthermore, luciferase reporter analysis revealed that miR-338-3p overexpression suppressed luciferase activity of WT-DSCAM-AS1 vector but not the mut-DSCAM-AS1. Ectopic expression of DSCAM-AS1 decreased miR-338-3p expression in the Siha cell. Overexpression of DSCAM-AS1 promoted cervical carcinoma cell growth and cycle via regulating miR-338-3p. These results suggested that DSCAM-AS1 functions as one oncogene through sponging miR-338-3p in cervical carcinoma.

Down-regulation of lncRNA LUADT1 suppresses cervical cancer cell growth by sequestering microRNA-1207-5p.

Emerging evidence has proved the essential roles of long non-coding RNAs (lncRNAs) in cervical carcinoma (CC). LncRNA lung adenocarcinoma-associated transcript 1 (LUADT1) is overexpressed and plays an oncogenic role in various cancers; however, the function and clinical values of LUADT1 in CC remain unclear. In this study we found that LUADT1 is highly expressed in CC tissues and cells. Up-regulated LUADT1 is significantly correlated with the more aggressive status and poorer survival of CC patients. studies show that LUADT1 depletion suppresses CC proliferation, and leads to cell apoptosis and cell cycle arrest. Furthermore, the xenograft mouse assay demonstrates that LUADT1 knockdown remarkably suppresses tumor growth. Mechanistically, LUADT1 binds to miR-1207-5p and inhibits miR-1207-5p expression in CC cells. Septin 9 (SEPT9) is identified as a miR-1207-5p target which is negatively regulated by LUADT1. Overexpression of SEPT9 abrogates the suppressed proliferation of CC cells induced by LUADT1 knockdown. These results demonstrate that LUADT1 sponges miR-1207-5p and consequently modulates SEPT9 expression in CC. Our study suggests the possible application of LUADT1 as a prognostic and therapeutic target to inhibit CC.

Tetramethylpyrazine inhibits the proliferation, invasiveness and migration of cervical cancer C33A cells by retarding the Hedgehog signaling pathway.

Cervical carcinoma (CC) ranks among the top four most common cancers in women worldwide. Over the last 10 years, several studies have confirmed the inhibitory effects of tetramethylpyrazine (TMP) on numerous types of cancer. To investigate the inhibitory effect of TMP on the CC C33A cell line, MTT and colony formation assays were performed to determine how TMP affects C33A cell survival and proliferation. Proliferation-, migration- and hedgehog (Hh) signaling pathway-related protein expression levels were analyzed via western blotting. Wound-healing and Transwell assays were used to detect the migration and invasion abilities of C33A cells, respectively. The results indicated that TMP markedly reduced the C33A cell survival rate compared with the cervical epithelial Ect1 cell line, which was unaffected by TMP treatment. C33A cell proliferation was downregulated by TMP treatment in a dose-dependent manner. TMP treatment also significantly inhibited C33A cell migration and invasiveness in a dose-dependent manner. Furthermore, TMP inhibited the Hh signaling pathway, as demonstrated by a dose-dependent reduction in Hh-related protein expression levels following TMP treatment. Subsequently, treatment with smoothened agonist increased the proliferation, invasiveness and migration abilities of TMP-treated C33A cells. In conclusion, TMP inhibited the proliferation, migration and invasiveness of CC cells via inhibition of the Hh signaling pathway.

Retraction notice to "MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5" [Canc. Lett. 322 (2012) 148-158

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Upon investigation, it was discovered that 4 out of 8 images contain fabrication. Fig. 6D, E, 8E and 7F have used the same microscopic image for different experimental settings. The Figure represented in 8E is the correct image placement. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

CHN1 promotes epithelial\u2013mesenchymal transition via the Akt/GSK-3\u03b2/Snail pathway in cervical carcinoma

BackgroundMetastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified.MethodsThe expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting.ResultsCHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002.ConclusionThese results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

MiR‑302c‑3p and miR‑520a‑3p suppress the proliferation of cervical carcinoma cells by targeting CXCL8.

The aim of the present study was to identify the differentially expressed microRNAs (miRs) in cervical carcinoma (CC) tissues and cells and to explore the function of miR-302c-3p and miR-520a-3p in the proliferation of CC cells. Potential dysregulated miRNAs in CC tissues and tumour-adjacent tissues were detected. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine the expression of miR-302c-3p, miR-520a-3p and CXCL8 in CC tissues and cell lines. The target genes of the miRNAs were predicted using miRTarBase and verified by luciferase reporter assays. RT-qPCR and western blotting were performed to measure the expression of C-X-C motif ligand (CXCL)8 after transfection. The effect on proliferation was verified by Cell Counting Kit assay and ethynyl-2-deoxyuridine staining. Flow cytometry was utilised to assess the effect on apoptosis. In the present study, miR-302c-3p and miR-520a-3p were markedly downregulated in CC cell lines compared to the normal cervical cell line H8. Functionally, overexpression of miR-302c-3p and/or miR-520a-3p inhibited proliferation and promoted the apoptosis of CC cell lines in vitro, while the knockdown of miR-302c-3p and/or miR-520a-3p had the opposite effect. Furthermore, miR-302c-3p and miR-520a-3p could both bind to CXCL8. Inhibition of CXCL8 in combination with miR-302c-3p and/or miR-520a-3p overexpression exerted proliferation-suppressive and apoptosis-stimulating effects on CC cells, whereas restoring CXCL8 attenuated the miR-302c-3p- and miR-520a-3p-induced anti-proliferative and pro-apoptotic effects. miR-302c-3p and miR-520a-3p suppress the proliferation of CC cells by downregulating the expression of CXCL8, which may provide a novel target for the treatment of CC.

NotoginsenosideR1 induces DNA damage via PHF6protein to inhibit cervical carcinoma cell proliferation.

Notoginsenoside R1 (NGR1), a monomer of Traditional Chinese medicine, is from the Panax notoginsenoside complex, and has been reported to inhibit the proliferation of various types of cancer. However the mechanism underlying NGR1-mediated inhibition of cervical carcinoma cell proliferation remains unclear. Therefore, the current study aimed to investigate the antitumor effects of NGR1 on cervical carcinoma cell lines (CaSki and HeLa cells) in vitro. The Cell Counting Kit-8 and soft agar cell colony formation assay results revealed that NGR1 suppressed the viability and the number colonies of CaSki and HeLa cells, respectively. Furthermore, the DAPI staining, flow cytometry and western blotting results revealed that NGR1 induced cervical carcinoma cell apoptosis, cell cycle arrest in the S phase, upregulation of cyclin A2 and CDK2 expression levels, and downregulation of cyclin D1 expression levels. To further investigate the mechanisms of NGR1, DNA-damage-related proteins, including H2A.X variant histone (H2AX), ATR serine/threonine kinase (ATR) and p53, and the nucleolus protein, plant homeodomain finger protein 6 (PHF6) were analyzed. The results indicated that NGR1 triggered the phosphorylation of H2AX and ATR in a dose- and time-dependent manner, and downregulated the expression level of PHF6 and upregulated the expression level of p53 in a dose- and time-dependent manner. In conclusion, the findings of the present indicated that NGR1 may inhibit the viability of cervical carcinoma cells and induce cell apoptosis via DNA damage, which may be activated by the downregulation of PHF6 expression levels, and the subsequent triggering of the phosphorylation of H2AX and ATR. In addition, NGR1 may exert an ability to arrest cervical carcinoma cells in the S phase and upregulate the expression levels of cyclin A2 and CDK2. Therefore, NGR1 may serve as a novel chemotherapeutic agent for cervical carcinoma.

Overexpression of FUBP1 is associated with human cervical carcinoma development and prognosis

AimsFar upstream element-binding protein 1 (FUBP1) has been shown to involve in the tumorigenesis and tumor progression of various cancers. However, the expression and function of FUBP1 in cervical carcinoma remains unknown. Main methodsTranscriptional expression of FUBP1 was initially evaluated using the Oncomine database, followed by evaluation of FUBP1 protein levels using immunohistochemistry in 119 cervical carcinoma patient tissues. In vitro experiments were performed to assess the tumorigenic role of FUBP1. Besides, Gene Set Enrichment Analysis, EnrichmentMap analysis, and protein-protein interaction (PPI) networks were used to evaluate the potential mechanisms of FUBP1 in promoting cervical cancer progression. Key fundingsIn this research, we found both FUBP1 mRNA transcription and protein expression levels increased significantly in cervical carcinoma tissues compared with adjacent normal cervical tissues. Furthermore, elevated FUBP1 expression was positively correlated with age, T classification, N classification, tumor recurrence, Ki67 expression, and poor prognosis in cervical carcinoma patients. Besides, elevated FUBP1 expression acted as an independent unfavorable predictor for overall survival and disease-free survival in cervical carcinoma. Overexpression of FUBP1 significantly promoted cervical carcinoma cell proliferation and inhibits cell apoptosis in vitro, while knockdown of FUBP1 showed the opposite effect. Mechanistically, bioinformatics analysis revealed that FUBP1 promoted the biological function of cervical carcinoma cells via enhancing DNA repair signal pathways. Our results demonstrate for the first time that FUBP1 is a novel prognostic factor and therapeutic target for cervical carcinoma.

Delivery of MicroRNA-let-7c-5p by Biodegradable Silica Nanoparticles Suppresses Human Cervical Carcinoma Cell Proliferation and Migration.

Human cervical cancer is the most common gynecological malignancy. The continuous development of nanotechnology has allowed the wide use of nanomaterials in cancer treatment. Nanoparticles can be used as gene carriers because of their surface effect and small-size effect. MicroRNA-let-7c-5p (miR-let-7c-5p) belongs to the let-7 family. Although it has been reported to exert a tumor suppressive effect in a variety of cancers, the exact role and mechanism of miR-let-7c-5p in the progression of cervical cancer are unclear. In this study, we synthesized flower-shaped SiO₂ -PEI nanoparticles with high pDNA/siRNA loading rates. This nanoparticle with miR-let-7c-5p-expressed plasmid could effectively transfer miR-let-7c-5p to human epithelial carcinoma (HeLa) cells. In addition, the combination of nanomaterials and gene therapy could inhibit the development of cancer under the conditions of extremely low cytotoxicity. These findings provided a new anticancer strategy based on F-SiO₂ -polyethyleneimine/miR-let-7c-5p (FSP-let-7c-5p)nanoparticles and indicated that miR-let-7c-5p/IGF-1R/PI3K/AKT and -catenin/SLUG could be used as new potential targets for the treatment of cervical cancer.

Abstract B36: Berberine induces apoptosis in cervical carcinoma cells by inducing DNA damage and inhibition of RAS MAPK pathway

Abstract Cervical cancer remains the leading cause of cancer mortality in females worldwide. Despite significant improvement in treatment modalities, the survival in advanced cervical cancer is still limited, resulting in poor survival. Berberine is an isoquinoline alkaloid isolated from Berberis vulgaris (barberry). Berberine is in focus for its preventive and therapeutic value in different cancers. Here we investigated how berberine modulated DNA damage response and survival pathway in cervical carcinoma cells. We carried out the current study in both HPV-positive and -negative cervical carcinoma cell lines. Our results indicate that berberine induced apoptosis in all the cervical carcinoma cells through activation of both caspase-dependent and -independent pathways. Berberine also induces accumulation of gamma H2AX foci in cervical carcinoma cells, which colocalized with proteins involved in DNA damage response, indicating accumulation of replication stress in berberine-treated cells. Berberine also repressed the proliferative RAS MAPK pathway, thereby reducing the proliferation of cervical carcinoma cells. Overall our data provide a novel insight into mechanism of berberine action in cervical carcinoma cells and underline its efficacy as a chemoadjuvant in treatment of cervical cancer. Citation Format: Komal Komal, Vidhya Athreyas, Shilpi Chaudhary, Mayank Singh. Berberine induces apoptosis in cervical carcinoma cells by inducing DNA damage and inhibition of RAS MAPK pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B36.

P16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis.

The Cyclin-Dependent Kinase Inhibitor p16 (p16) acts as a tumor suppressor in most cells, but for HPV transformed cervical cancer, in which oncoprotein E7 expressed by human papillomavirus (HPV) mediates the degradation of retinoblastoma protein (Rb), p16 exhibits oncogenic activity. Our study was conducted to study the mechanism underling p16 mediated promoting effect of cell proliferation in cervical cancer cell lines. CCK8 assay and EdU incorporation were conducted to evaluate cell proliferation. Loss-of-function assay was used to silence p16 in Ca Ski and SiHa cells. Next, western blot, qPCR, RNA silencing, luciferase activity assay, run-on assay, mRNA stability assay, RNA immunoprecipitation, co-immunoprecipitation Immunofluorescence were performed to examine the interaction between CDK6, HuR, and IL1A mRNA in p16 mediated proliferation promoting effect. Our results showed that: (1) Silencing p16 inhibited the proliferation of cervical cancer cells by decreasing the half-life of IL1A mRNA in CDK6 dependent manner; (2) The stabilization of IL1A mRNA was regulated by HuR which could be inactivated by p16/CDK6 mediated phosphorylation at Ser202; (3) IL1A mediated the oncogenic activity of p16 in cervical carcinoma cell lines. In conclusion, p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis.

ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability.

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = −0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3′UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

Baicalein blocked cervical carcinoma cell proliferation by targeting CCND1 via Wnt/β-catenin signaling pathway

The purpose of this study was to investigate the inhibitory effect of baicalein on the proliferation of cervical carcinoma cells and stimulate cervical carcinoma cells with baicalein. MTT method was used to observe cell proliferation. Flow cytometry was used to observe cell cycle, and gene technology was used to observe the expression of corresponding genes at the level of gene and protein. β-catenin activity was assessed using Western blot and ChIP. Baicalein suppressed cervical carcinoma cell HeLa proliferation by enhancing the activity of caspase-3. Baicalein blocked cell cycle at G0/G1 stage by inhibiting the expression of some genes. At the same time, it can prevent the nuclear translocation of β-catenin and inhibit the activity of Wnt. When the Wnt signaling pathway is increased, the proliferation of HeLa cells is inhibited, and apoptosis is promoted in this way. In conclusion, it indicated that baicalein inhibits cervical carcinoma progression by targeting CCND1 via Wnt/β-catenin signaling pathway.

Isoflurane promotes proliferation and invasion of cervical carcinoma cells via downregulation of miR-375 expression

Isoflurane promotes proliferation and invasion of cervical carcinoma cells via downregulation of miR-375 expression

MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1.

MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367 cluster has been reported to suppress the proliferation of cervical carcinoma cells through the novel target AKT1; however, the molecular mechanism of miR-302 in cervical cancer metastasis remains unclear. The present study aimed to investigate the clinical significance of miR-302-3p expression in cervical cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant phenotypes of cervical cancer cells. The present data indicated that miR-302-3p was significantly downregulated in cervical cancer tissues compared with the level in adjacent non-tumor tissues, and low expression of miR-302-3p was significantly associated with node metastasis, advanced clinical stage, and poor prognosis in patients with cervical cancer. Restoration of miR-302-3p expression caused a significant reduction in cervical cancer cell migration and invasion. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally, overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in cervical cancer tissues compared with the levels in adjacent tissues, and its high expression was associated with node metastasis, advanced clinical stage, and shorter survival time in patients with cervical cancer. Notably, a negative correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues was observed. Taken together, the present study suggests that miR-302-3p serves a suppressive role in cervical cancer metastasis, partly at least, via directly targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic target for cervical cancer treatment.

Ellagic acid induces HeLa cell apoptosis via regulating signal transducer and activator of transcription 3 signaling.

Ellagic acid has been reported to possess various activities, including anti-inflammatory, anti-oxidative, antiviral and anticancer abilities. However, the effect and underlying molecular mechanism of ellagic acid on cervical carcinoma remain unclear. Therefore, the present study aimed to investigate the effects of ellagic acid on human cervical carcinoma cells and the molecular mechanism involved. The present study assessed the survival of HeLa cells cultured in vitro using an MTT assay. Apoptosis rate and cell cycle of HaLa cells were measured using an Annexin V-Fluorescein isothiocyanate/propidium iodide Apoptosis Detection and Cell Cycle Analysis kits, respectively, following treatment with varying concentrations of ellagic acid. Further effects of ellagic acid on HeLa cells was assessed using flow cytometry and western blotting. Ellagic acid treatment significantly inhibited cell proliferation of the human cervical carcinoma HeLa, SiHa and C33A cells. In HeLa cells, it was observed that ellagic acid arrested the cell cycle at G1 phase, induced cell apoptosis, suppressed the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 (STAT3), as well as modulated the expression of associated proteins. Collectively, the results of the present study provide evidence that ellagic acid inhibits cervical carcinoma cell proliferation, and induces apoptosis and cell cycle arrest at G1 phase possibly via the regulation of STAT3 signaling.