Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin

Deng, Min; Sun, Jin; Xie, Shuanshuan; Zhou, Hui; Wang, Yanchun; Zhong, Ailing; Zhang, Hongqin; Lu, Renquan; Guo, Lin

doi:10.3892/mmr.2019.10477

Cited by 27 publications

(28 citation statements)

References 48 publications

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“…MCM2 is a component of the replicative helicase machinery that is capable of interacting with histones H3 and H4 via the N-terminal domain in the process of replication [ 15 ]. MCM2 can increase the sensitivity of ovarian cancer cells to carboplatin through p53-dependent apoptotic response, thereby improving the therapeutic application of carboplatin in ovarian cancer patients [ 16 ]. Besides, extent of HMGA1 phosphorylation has been found to be differentially expressed in response to MCM2 perturbation and has a significant role to play in modulating cell behaviors of lung cancer cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Wang

Guo²,

Zhou

et al. 2020

J Exp Clin Cancer Res

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Background Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Methods Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. Results We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Conclusions Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Wang

Guo²,

Zhou

et al. 2020

J Exp Clin Cancer Res

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“…Recent research suggested that MCM2 might be a potential therapeutic target for HCC [ 26 ]. Furthermore, Deng et al found that MCM2 inhibition could increase the sensitivity of carboplatin in ovarian cancer cell [ 27 ]. MCM3 had similarly a high expression level in multiple cancer types, such as osteosarcoma [ 21 ], salivary gland tumors [ 28 ], and glioma [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of the DNA Replication Regulator MCM Complex Expression and Prognostic Significance in Hepatic Carcinoma

Cao

Wang

et al. 2020

BioMed Research International

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Background. The microliposome maintenance (MCM) complex, MCM2-7, is revealed to be involved in multiple cellular processes and plays a key role in the development and progression of human cancers. However, the MCM complex remains poorly elaborated in hepatic carcinoma (HCC). Methods. In the study, we found the mRNA and protein level by bioinformatics. We also explored the prognostic value, genetic alteration, interaction network, and functional enrichment of MCM2-7. The MCM expression and correlation among these MCMs in HCC cell lines were identified by western blot. Results. MCM2-7 was significantly increased in HCC tissues compared to normal liver tissues. The high level of MCM2-7 had a positive correlation with poor prognosis. However, MCM2-7 alterations were not correlated with poor OS. MCMs were both increased in HCC cell lines compared to the normal hepatocyte cell line. Furthermore, the positive correlation was found among MCMs in HCC cell lines. Conclusions. The MCM complex was increased in HCC tissues and cell lines and negatively correlated with prognosis, which might be important biomarkers for HCC.

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“… 45 In other types of cancers such as ovarian and lung cancer, MCM2 was found to promote the proliferative potential of these cancer cells. 46 , 47 In our in vitro functional studies, we consistently showed that MCM2 knockdown suppressed the proliferation of HeLa and SiHa cells, suggesting that MCM2 may play an oncogenic role in the cervical cancer progression. However, the prognostic role of MCM2 in cervical cancer is still controversial among studies, as a high expression of MCM2 showed better prognosis for patients with cervical cancer as shown in our bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 68%

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies

Han

Sun

et al. 2021

CMAR

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Background: Cervical cancer belongs to one of the most common female cancers; yet, the exact underlying mechanisms are still elusive. Recently, microarray and sequencing technologies have been widely used for screening biomarkers and molecular mechanism discovery in cancer studies. In this study, we aimed to analyse the microarray datasets using comprehensive bioinformatics tools and identified novel biomarkers associated with the prognosis of patients with cervical cancer. Methods: The differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) datasets including GSE138080, GSE113942 and GSE63514 were analysed using GEO2R tool. The functional enrichment analysis was performed using g:Profiler tool. The protein-protein interaction (PPI) network construction and hub genes identification were performed using the STRING database and Cytoscape software, respectively. The hub genes were subjected to expression and survival analysis in the cervical cancer. The EdU incorporation and Cell Counting Kit-8 assays were performed to evaluate the effects of hub gene knockdown on the proliferation of cervical cancer cells. Results: A total of 89 overlapping DEGs (63 up-regulated and 26 down-regulated genes) were identified in the microarray datasets. The functional enrichment analysis indicated that the overlapping DEGs were mainly associated with "DNA replication" and "cell cycle". Furthermore, the PPI network analysis revealed that the network contains 87 nodes and 309 edges. Sub-module analysis using the Molecular Complex Detection tool identified 21 hub genes from the PPI network. The expression levels of the 21 hub genes were all up-regulated in the cervical cancer tissues when compared to normal cervical tissues as analysed by GEPIA tool. The survival analysis showed that the low expression of cell division cycle 45 (CDC45), GINS complex subunit 2 (GINS2), minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen (PCNA) was significantly correlated with the shorter overall survival of patients with cervical cancer. Moreover, the protein expression levels of GINS2, MCM2 and PCNA, but not CDC45, were significantly upregulated in the cervical cancer tissues when compared to normal cervical tissues. Finally, knockdown of MCM2 significantly suppressed the proliferation of HeLa and SiHa cells. Conclusion:In conclusion, we screened a total of 89 overlapping DEGs from the GEO datasets, and further analysis identified four hub genes (CDC45, GINS2, MCM2 and PCNA) that were likely associated with the prognosis of patients with cervical cancer. MCM2 knockdown repressed the cervical cancer cell proliferation. The current findings may provide novel insights into understanding the pathophysiology of cervical cancer and develop therapeutic targets for patients with cervical cancer.

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Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin

Cited by 27 publications

References 48 publications

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Identification of the DNA Replication Regulator MCM Complex Expression and Prognostic Significance in Hepatic Carcinoma

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies

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