Identification of upregulated genes in oral squamous cell carcinomas

Lessa, Roberta Cardim; Campos, Antônio Hugo José Fróes Marques; Freitas, Carlos Elias de; Silva, Felipe Rodrigues da; Kowalski, Luiz Paulo; Carvalho, André L.; Vettore, André Luiz

doi:10.1002/hed.23169

Cited by 38 publications

(26 citation statements)

References 30 publications

(56 reference statements)

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“…Another report of POLQ expression in early breast cancer found the highest POLQ expression in ER negative and high-grade tumors; higher expression was correlated with shorter relapse-free survival times [83]. POLQ is one of the genes frequently upregulated in a group of oral squamous cell carcinomas from Brazil [84]. In a study of early to mid-stage non small-cell lung cancers, higher expression of a five-gene prognostic signature including POLQ was associated with poor outcome [85].…”

Section: Polq and Cancermentioning

confidence: 99%

DNA polymerase θ (POLQ), double-strand break repair, and cancer

2016

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DNA polymerase theta (pol θ) is encoded in the genomes of many eukaryotes, though not in fungi. Pol θ is encoded by the POLQ gene in mammalian cells. The C-terminal third of the protein is a family A DNA polymerase with additional insertion elements relative to prokaryotic homologs. The N-terminal third is a helicase-like domain with DNA-dependent ATPase activity. Pol θ is important in the repair of genomic double-strand breaks (DSBs) from many sources. These include breaks formed by ionizing radiation and topoisomerase inhibitors, breaks arising at stalled DNA replication forks, breaks introduced during diversification steps of the mammalian immune system, and DSB induced by CRISPR-Cas9. Pol θ participates in a route of DSB repair termed “alternative end-joining” (altEJ). AltEJ is independent of the DNA binding Ku protein complex and requires DNA end resection. Pol θ is able to mediate joining of two resected 3’ ends harboring DNA sequence microhomology. “Signatures” of Pol θ action during altEJ are the frequent utilization of longer microhomologies, and the insertion of additional sequences at joining sites. The mechanism of end-joining employs the ability of Pol θ to tightly grasp a 3’ terminus through unique contacts in the active site, allowing extension from minimally paired primers. Pol θ is involved in controlling the frequency of chromosome translocations and preserves genome integrity by limiting large deletions. It may also play a backup role in DNA base excision repair. POLQ is a member of a cluster of similarly upregulated genes that are strongly correlated with poor clinical outcome for breast cancer, ovarian cancer and other cancer types. Inhibition of pol θ is a compelling approach for combination therapy of radiosensitization.

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Section: Polq and Cancermentioning

confidence: 99%

DNA polymerase θ (POLQ), double-strand break repair, and cancer

2016

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“…Although overexpression ALDOA has been discovered in many tumors [9], the ultimate mechanisms are undetermined and discordant. It has been assumed that ALDOA expression increased because glycolysis is faster in rapidly evolving tumor cells than in normal tissues as an enzyme [10].…”

Section: Introductionmentioning

confidence: 99%

miR-122-5p Inhibits the Proliferation, Invasion and Growth of Bile Duct Carcinoma Cells by Targeting ALDOA

Liu

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bile duct cancer, although not among the most common tumors, still accounts for more and more worldwide deaths each year. By attempting to verify an overexpression of ALDOA in cholangiocarcinoma tissues and cells and explore the underlying molecular mechanism regulated by miR-122-5p, this study was designed to provide a potential molecular target in bile duct cancer treatment. Methods: Western blot and immunohistochemistry were performed to detect the ALDOA protein level in duct carcinoma tissues. The transfection efficiency was confirmed by western blot and/or RT-qPCR assay. The proliferation of bile duct carcinoma cells was determined by MTT and colony formation assay. The invasion ability of bile duct carcinoma cells was evaluated with Transwell invasion assay. Flow cytometry detected cell apoptosis of bile duct carcinoma cells. The miRNAs which modulate ALDOA were filtrated from bioinformatics software and clinical specimens. The target relationship was confirmed by dual luciferase reporter assay. Furthermore, a xenograft model was completed to verify the impact of miRNA on inhibition growth of bile duct carcinoma cells. Results: ALDOA was found up-regulated in bile duct carcinoma tissues and cells. Knockdown of ALDOA promoted the apoptosis of cells and inhibited the proliferation and invasion of bile duct carcinoma cells. Bioinformatics and clinical specimens indicated the negative correlation and targeted regulation between miR-122-5p and ALDOA. By down-regulating ALDOA, overexpression of miR-122-5p appeared to promote cell apoptosis and significantly inhibit cell proliferation, invasion in vitro and suppress the tumor growth in vivo. Conclusion: miR-122-5p inhibited proliferation and invasion of bile duct carcinoma cells and promoted cell apoptosis by targeting ALDOA expression.

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“…Thus far, data mining has been widely used in the medical assessment of various cancer types. For instance, Roberta et al found 40 genes that are up-regulated in HNSCC using ORESTES data mining analysis [12]. Zainab Abu Bakar et al constructed a framework for the diagnosis of the tumor stage of primary oral cancer by using data mining of Bayesian reasoning [13].…”

Section: Introductionmentioning

confidence: 99%

Predicting postoperative complications of head and neck squamous cell carcinoma in elderly patients using random forest algorithm model

Chen

Cao

Gao

et al. 2015

BMC Med Inform Decis Mak

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BackgroundHead and Neck Squamous Cell Carcinoma (HNSCC) has a high incidence in elderly patients. The postoperative complications present great challenges within treatment and they're hard for early warning.MethodsData from 525 patients diagnosed with HNSCC including a training set (n = 513) and an external testing set (n = 12) in our institution between 2006 and 2011 was collected. Variables involved are general demographic characteristics, complications, disease and treatment given. Five data mining algorithms were firstly exploited to construct predictive models in the training set. Subsequently, cross-validation was used to compare the different performance of these models and the best data mining algorithm model was then selected to perform the prediction in an external testing set.ResultsData from 513 patients (age > 60 y) with HNSCC in a training set was included while 44 variables were selected (P < 0.05). Five predictive models were constructed; the model with 44 variables based on the Random Forest algorithm demonstrated the best accuracy (89.084 %) and the best AUC value (0.949). In an external testing set, the accuracy (83.333 %) and the AUC value (0.781) were obtained by using the random forest algorithm model.ConclusionsData mining should be a promising approach used for elderly patients with HNSCC to predict the probability of postoperative complications. Our results highlighted the potential of computational prediction of postoperative complications in elderly patients with HNSCC by using the random forest algorithm model.

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Identification of upregulated genes in oral squamous cell carcinomas

Cited by 38 publications

References 30 publications

DNA polymerase θ (POLQ), double-strand break repair, and cancer

DNA polymerase θ (POLQ), double-strand break repair, and cancer

miR-122-5p Inhibits the Proliferation, Invasion and Growth of Bile Duct Carcinoma Cells by Targeting ALDOA

Predicting postoperative complications of head and neck squamous cell carcinoma in elderly patients using random forest algorithm model

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