scholarly journals Histone Deacetylation Regulated by KDM1A to Suppress DACT1 in Proliferation and Migration of Cervical Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lingjuan Zeng ◽  
Chunyan Chen ◽  
Chanjiao Yao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Histone Deacetylation ◽  
Cervical Cancer Cell ◽  
Migration Ability ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Objective. Increased expression of KDM1A and decreased expression of DACT1 in cervical cancer cells were noticed in a previous study. This study is aimed at exploring the mechanism behind the KDM1A regulation on DACT1 in cervical cancer cells. Methods. The expression profile of KDM1A and DACT1 in cervical cancer tissues was searched in TCGA database. In vitro experiments verified the effect of KDM1A and DACT1 on proliferation and migration ability of cervical cancer cell lines after cell transfection. The interaction of KDM1A with HDAC1 was identified by coimmunoprecipitation (Co-IP). The expression levels of KDM1A and DACT1 in cervical cancer cell lines were determined by qRT-PCR and western blot. Results. TCGA database showed that cervical cancer tissues had elevated expression of KDM1A and decreased expression of DACT1, which was consistent with the observation in cervical cancer cell lines. KDM1A was found to negatively regulate DACT1 through histone deacetylation. Meanwhile, the downregulation of KDM1A or overexpression of DACT1 could suppress the cell proliferation and migration ability in HeLa and SiHa cells. Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression. Conclusion. KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.

scholarly journals Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1934 ◽  
Author(s):  
Eric Ehrke-Schulz ◽  
Sonja Heinemann ◽  
Lukas Schulte ◽  
Maren Schiwon ◽  
Anja Ehrhardt
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adenoviral Vectors ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
Adenoviral Delivery ◽  
Cervical Cancer Cells

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.

LncRNA SNHG1 enhances cell proliferation, migration, and invasion in cervical cancer

2018 ◽  
Vol 96 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Yang Liu ◽  
Yanling Yang ◽  
Lei Li ◽  
Yuan Liu ◽  
Peng Geng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Knock Down ◽  
Cervical Cancer Cells

Objective: This study investigated the effects of lncRNA SNHG1 on the proliferation, migration, and invasiveness of cervical cancer cells. Methods: Three pairs of cervical cancer tissue samples and their corresponding adjacent samples were analyzed using Human LncRNA Microarray V3.0 chip for differential analysis. The expression of SNHG1 in cervical cancer cell lines was verified by qRT–PCR. CCK8 assays and colony formation assays were used to study the changes in cell proliferation. Cell migration and Transwell assays were used to study changes in cell migration and invasiveness. Results: SNHG1 was highly expressed in cervical cancer tissues and cervical cancer cell lines. SNHG1 siRNA could knock-down the expression level of SNHG1 in cervical cancer cell lines HeLa and C33-A. After knock-down of SNHG1, cell proliferation and migration as well as invasiveness in HeLa and C-33A cells decreased. Conclusion: LncRNA SNHG1 promotes the development of cervical cancer cells.

Human Papillomavirus E7 Oncoprotein Promotes Proliferation and Migration through the Transcription Factor E2F1 in Cervical Cancer Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Sijuan Tian ◽  
Li Zhang ◽  
Yang Li ◽  
Di Cao ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Wild Type ◽  
Migration Ability ◽  
E7 Oncoprotein ◽  
Hpv E7 ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration ◽  
Transcription Factor E2f1

Background: High-risk human papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the risk of cervical cancer among Asian populations. Objective: This study aimed to determine whether the HPV58 E7 T20I (C632T) variant promotes the malignant behavior of cervical cancer cells and the underlying mechanism of the HR-HPV E7 oncoprotein involved in the development of cervical cancer. Methods: CCK-8 and clone formation assays were used to detect cell proliferation ability. Transwell assays and cell wound healing assays were used to evaluate cell migration ability. Targeted knockdown of E2F1 expression using specific siRNA, RT-qPCR and Western blot were performed to assess gene expression changes. A chromatin immunoprecipitation assay was used to verify that E2F1 interacted with the TOP2A promoter region. Results: HPV58 E7 and HPV58 E7M oncoproteins increased the proliferation and migration ability of cervical cancer cells. However, the HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. HPV E7 and E7M oncoproteins increased the expression of TOP2A, BIRC5 and E2F1, and knockdown of HPV E7 decreased their expression. Low E2F1 expression reduced the expression of TOP2A and BIRC5 and inhibited the proliferation and migration ability of cervical cancer cells. E2F1 interacted with the TOP2A gene promoter region to promote its transcriptional expression. Conclusions: The HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. The HR-HPV E7 oncoprotein enhanced the proliferation and migration of cervical cancer cells, which was considered to be due to the HPV E7 oncoprotein increasing the expression of BIRC5 and TOP2A by upregulating the transcription factor E2F1.

Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines

2016 ◽  
Vol 94 (5) ◽  
pp. 526-533 ◽  
Author(s):  
Yan Zhao ◽  
Xinyu Wang ◽  
Lei Li ◽  
Changzhong Li
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Cervical Cancer Cells

The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

scholarly journals Proteomics Analysis of Andrographolide-Induced Apoptosis Via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines

2021 ◽  
Vol 22 (13) ◽  
pp. 6806
Author(s):  
Pariyakorn Udomwan ◽  
Chamsai Pientong ◽  
Panwad Tongchai ◽  
Ati Burassakarn ◽  
Nuchsupha Sunthamala ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
World Population ◽  
Cervical Cancer Cells

Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions.

scholarly journals Anti-Silencing Function 1B Overexpression Affects Prognosis and Promotes Invasion in Cervical Carcinoma via Activation of Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Weijing Zhang ◽  
Han Li ◽  
Xiaoying Sun ◽  
Yongjie Shi ◽  
Yadi Yang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Western Blotting ◽  
Cervical Carcinoma ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Clinicopathological Parameters ◽  
Cervical Cancer Cells

Abstract Background: Anti-silencing function 1B histone chaperone (ASF1B) has been identified to compensate for growth defects and sensitivity to replication stress. Recent studies demonstrated that ASF1B plays an important role in the tumorigenesis of human cancer. However, its relationship with clinical outcome of cervical carcinoma is unknown. Therefore, we aimed to investigate the expression pattern and clinical significance of ASF1B in cervical cancer and its role in regulating invasion and metastasis of cervical cancer cell lines.Methods: Expression of ASF1B was analyzed in eight cervical cancer cell lines, and eight pairs of cervical cancer samples and the adjacent normal specimens, using real-time PCR and western blotting. Immunohistochemistry was used to analyze ASF1B expression in paraffin-embedded tissues from 147 cervical cancer patients. The association between ASF1B expression levels, clinicopathological parameters, and prognosis was analyzed statistically. Moreover, the biological function and potential mechanism of ASF1B in migration and invasion of cervical cancer cells were investigated by in vitro experiments and Western blotting.Results: ASF1B mRNA and protein levels were overexpressed in cervical cancer cell lines and tissues compared with normal cells and adjacent normal cervical specimens. In paraffin-embedded cervical carcinoma tissues, upregulation of ASF1B protein was identified in 86 (58.5%) of 147 cases, and was remarkably associated with pelvic lymph node metastasis, lymphovascular space involvement, property of surgical margin, FIGO stage, sqaumous cell carcinoma antigen and poor survival. Cox analysis demonstrated that ASF1B expression was an independent risk predictor for survival in patients with cervical carcinoma. Additionally, down-regulation of ASF1B significantly inhibited invasion and migration of cervical cancer cells. Moreover, it was demonstrated that ASF1B regulated the Wnt/β-catenin pathway in cervical carcinoma.Conclusions: This study suggested that ASF1B might serve as a important prognostic biomarker and therapeutic target for patients with cervical carcinoma.

scholarly journals Long Noncoding RNA GAS5, Which Acts as a Tumor Suppressor via microRNA 21, Regulates Cisplatin Resistance Expression in Cervical Cancer

2017 ◽  
Vol 27 (6) ◽  
pp. 1096-1108 ◽  
Author(s):  
Qirong Wen ◽  
Yan Liu ◽  
Huabing Lyu ◽  
Xiaying Xu ◽  
Qingxia Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cisplatin Resistance ◽  
Cervical Cancer Cell ◽  
Cancer Tissue ◽  
Cervical Cancer Tissue ◽  
Cervical Cancer Cells

ObjectivesThe aims of this study were to investigate the functions of GAS5 as a tumor suppressor in cervical cancer and explore the mechanism.MethodsThe expression of GAS5 and microRNA 21 (miR-21) was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. We identified the interaction of GAS5 and miR-21 by quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter assay. We also studied the functions of GAS5 in proliferation, apoptosis, migration, and invasion in cervical cancer cells in vitro and vivo. Finally, the impact of GAS5 on cisplatin resistance and its mechanism in cervical cancer cells was also identified.ResultsThe expression of GAS5 and miR-21 was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. GAS5, which is a tumor suppressor playing roles in inhibiting the malignancy of cervical cancer cells, including proliferation in vivo and vitro, migration, and invasion, has a low expression in cervical cancer tissue and cervical cancer cell lines, whereas miR-21 expression is high. GAS5 significantly decreased the expression of miR-21, and there is a reciprocal repression of gene expression between GAS5 and miR-21. Besides, most importantly, we found that high expression of GAS5 and low expression of miR-21 can enhance the sensitivity of SiHa/cDDP cancer cells to cisplatin. A further experiment for identifying the mechanism of cisplatin resistance by GAS5 showed that GAS5 can not only regulate phosphatase and tensin homolog through miR-21 but also influence the phosphorylation of Akt.ConclusionsOur results indicate that GAS5 is a direct target of miR-21 and can predict the clinical staging of cervical cancer. Most importantly, GAS5 can also influence cisplatin resistance in cervical cancer via regulating the phosphorylation of Akt. All of these suggest that GAS5 may be a novel therapeutic target for treating cervical cancer.

scholarly journals Cytotoxic Effect of Disulfiram/Copper On Human Cervical Cancer Cell Lines and LGR5-Positive Cancer Stem-Like Cells

2021 ◽  
Author(s):  
Hao-Zhe Cao ◽  
Peng-Sheng Zheng ◽  
Wen-Ting Yang
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Dependent Manner ◽  
Cu Complex ◽  
Cervical Cancer Cells

Abstract Background: Tumor resistance is a global challenge for tumor treatment. Cancer stem cells (CSCs) are the main population of tumor cells for drug resistance. We have reported that high aldehyde dehydrogenase (ALDH) activity represents a functional marker for cervical CSCs. Here we aim at disulfiram (DS), an ALDH inhibitor, that has the potential as a novel treatment to be used for cervical cancer.Methods: MTT assay, western blot, FCS analysis and sorting, vector construction and transfection, in vivo anti-tumor assays were performed using cervical cancer cell lines SiHa and HeLa. Cell cycle distribution and cell apoptosis were carried out by flow cytometry. The cytotoxicity of DS was detected by MTT assay and a xenograft cervical cancer model. Results: Disulfiram was cytotoxic to cervical cancer cell lines in a copper (Cu)-dependent manner. Disulfiram/copper (DS/Cu) complex induced deregulation of S-phase and inhibited the expression of stemness marker in cervical cancer cells. DS/Cu caused the death of LGR5-positive cervical cancer cells, a cancer stem-like cell population, which lead to cisplatin resistance in cervical cancer cells. Furthermore, DS/Cu complex had the greater antitumor efficacy on cervical cancer than cisplatin group in vitro and in vivo. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu complex may be superior to cisplatin because of targeting LGR5-positive cervical cancer stem-like cells in cervical cancer. Thus, the DS/Cu complex may represent a potential therapeutic strategy for cervical cancer patients.

scholarly journals Four electrode-based impedimetric biosensors for evaluating cytotoxicity of tamoxifen on cervical cancer cells

RSC Advances ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 798-806
Author(s):  
Rangadhar Pradhan ◽  
Ashish Kalkal ◽  
Shlok Jindal ◽  
Gopinath Packirisamy ◽  
Sanjeev Manhas
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Cervical Cancer Cells

In the current study, novel four electrode-based impedimetric biosensors have been fabricated using photolithography techniques and utilized to evaluate the cytotoxicity of tamoxifen on cervical cancer cell lines.

scholarly journals The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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