Overexpression of <scp>DNA </scp><i>polymerase iota</i> (<scp><i>Polι</i></scp>) in esophageal squamous cell carcinoma

Zhou, Jundong; Zhang, Shuyu; Xie, Ling; Liu, Pengfei; Xie, Fang; Wu, Jinchang; Cao, Jianping; Ding, Wei

doi:10.1111/j.1349-7006.2012.02309.x

Cited by 39 publications

(30 citation statements)

References 29 publications

(28 reference statements)

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“…Genomic DNA was extracted from cells using the SDS and proteinase K methods and then subjected to sodium bisulfite treatment as reported previously 21,22. The converted DNA was subjected to analysis via the Illumina Infinium Human Methylation 450K BeadChip by Genergy Biotech (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Luo¹,

Wang²,

Tang³

et al. 2017

J. Cancer

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Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy.

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Section: Methodsmentioning

confidence: 99%

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Luo¹,

Wang²,

Tang³

et al. 2017

J. Cancer

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“…For instance Malkas' group identified an elevated expression of Pol ι in human breast cancer cells, which was correlated with decreased DNA replication fidelity [20]. We have recently demonstrated that the expression of Pol ι is upregulated in ESCC tissues [21, 22] and that the dysregulation of Pol ι harasses cell cycle progression through enhancing cyclin D1 expression [22]. However, the relationship between Pol ι expression and tumor invasion and metastasis of ESCC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

et al. 2016

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DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

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“…Determining how these bacterial enzymes are regulated will allow a better description of the regulation of TLS polymerase activity in other systems. Furthermore, TLS polymerases have been implicated in the evolution of antibiotic resistance in bacteria and cancer in humans (24)(25)(26)(27). Deregulation of TLS polymerases, therefore, has a variety of deleterious consequences in both prokaryotic and eukaryotic organisms.…”

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confidence: 99%

A Single Residue Unique to DinB-Like Proteins Limits Formation of the Polymerase IV Multiprotein Complex in Escherichia coli

Cafarelli¹,

Rands²,

Benson³

et al. 2013

Journal of Bacteriology

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The activity of DinB is governed by the formation of a multiprotein complex (MPC) with RecA and UmuD. We identified two highly conserved surface residues in DinB, cysteine 66 (C66) and proline 67 (P67). Mapping on the DinB tertiary structure suggests these are noncatalytic, and multiple-sequence alignments indicate that they are unique among DinB-like proteins. To investigate the role of the C66-containing surface in MPC formation, we constructed the dinB(C66A) derivative. We found that DinB(C66A) copurifies with its interacting partners, RecA and UmuD, to a greater extent than DinB. Notably, copurification of RecA with DinB is somewhat enhanced in the absence of UmuD and is further increased for DinB(C66A). In vitro pulldown assays also indicate that DinB(C66A) binds RecA and UmuD better than DinB. We note that the increased affinity of DinB(C66A) for UmuD is RecA dependent. Thus, the C66-containing binding surface appears to be critical to modulate interaction with UmuD, and particularly with RecA. Expression of dinB(C66A) from the chromosome resulted in detectable differences in dinBdependent lesion bypass fidelity and homologous recombination. Study of this DinB derivative has revealed a key surface on DinB, which appears to modulate the strength of MPC binding, and has suggested a binding order of RecA and UmuD to DinB. These findings will ultimately permit the manipulation of these enzymes to deter bacterial antibiotic resistance acquisition and to gain insights into cancer development in humans.

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Overexpression of DNA polymerase iota (Polι) in esophageal squamous cell carcinoma

Cited by 39 publications

References 29 publications

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

A Single Residue Unique to DinB-Like Proteins Limits Formation of the Polymerase IV Multiprotein Complex in Escherichia coli

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