MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells

Liu, Yangbo; He, Gang; Wang, Yan; Guan, Xinging; Pang, Xiaowu; Zhang, Bo

doi:10.1016/j.toxlet.2013.05.643

Cited by 57 publications

(48 citation statements)

References 26 publications

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“…Similar results were reported where inhibition of MCM2 by RNAi produces apoptotic response in P53+ and P53− cancer cell lines but causes G1 arrest in normal cells [121]. Trichostatin A and siRNA mediated downregulation of MCM2 generated apoptotic response in HCT116 cells [122]. Knocking down MCM7 not only inhibits cell proliferation in glioblastoma multiforme tumor cells but also prevents tumor growth in mouse models of glioblastoma multiforme [123].…”

Section: MCM Expression and Cancersupporting

confidence: 72%

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

Das

Singh

Pradhan

et al. 2014

Molecular Biology International

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As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.

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Section: MCM Expression and Cancersupporting

confidence: 72%

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

Das

Singh

Pradhan

et al. 2014

Molecular Biology International

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“…TOP2A is targeted by etoposide (30). ASNS is targeted in asparginase therapy of acute lymphoblastic leukemia (31), and both MKI67 and MCM2 have been studied as biomarkers (32) and (33) and potential drug targets (34,35). Targeting these genes is likely to bring therapeutic value to many patients as they are recurrently upregulated across many cancer types.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers

Kaczkowski¹,

Tanaka

Kawaji

et al. 2016

Cancer Research

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Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.Cancer Res; 76(2); 216-26. Ó2015 AACR.

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“…RT-PCR showed that MCM2 gene expression is downregulated upon TSA treatment and that knockdown of Mcm2 induces cellular apoptosis in colon cancer cells. This downregulation of MCM2 was dependent on TSA-mediated changes in the JNK signaling pathway [123]. …”

Section: Small Molecule Inhibitors and Potential Chemotherapeutic mentioning

confidence: 99%

The Mcm2-7 Replicative Helicase: A Promising Chemotherapeutic Target

Simon

Schwacha

2014

BioMed Research International

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Numerous eukaryotic replication factors have served as chemotherapeutic targets. One replication factor that has largely escaped drug development is the Mcm2-7 replicative helicase. This heterohexameric complex forms the licensing system that assembles the replication machinery at origins during initiation, as well as the catalytic core of the CMG (Cdc45-Mcm2-7-GINS) helicase that unwinds DNA during elongation. Emerging evidence suggests that Mcm2-7 is also part of the replication checkpoint, a quality control system that monitors and responds to DNA damage. As the only replication factor required for both licensing and DNA unwinding, Mcm2-7 is a major cellular regulatory target with likely cancer relevance. Mutations in at least one of the six MCM genes are particularly prevalent in squamous cell carcinomas of the lung, head and neck, and prostrate, and MCM mutations have been shown to cause cancer in mouse models. Moreover various cellular regulatory proteins, including the Rb tumor suppressor family members, bind Mcm2-7 and inhibit its activity. As a preliminary step toward drug development, several small molecule inhibitors that target Mcm2-7 have been recently discovered. Both its structural complexity and essential role at the interface between DNA replication and its regulation make Mcm2-7 a potential chemotherapeutic target.

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MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells

Cited by 57 publications

References 26 publications

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers

The Mcm2-7 Replicative Helicase: A Promising Chemotherapeutic Target

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