Gene expression changes associated with chemotherapy resistance in Ewing sarcoma cells

Horbach, Leonardo; Sinigaglia, Marialva; Silva, Camila Alves da; Olguins, Danielly Brufatto; Gregianin, Lauro José; Brunetto, Algemir Lunardi; Brunetto, André T.; Roesler, Rafaël; Farias, Caroline Brunetto de

doi:10.3892/mco.2018.1608

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…The expression of these genes remained constant after different doses and radiotherapy periods, yet there are no studies in GBM and other cancers related to expression changes of these genes due to radiotherapy. However, a similar study in sarcoma has identified several genes implicated in chemoresistance [41]. Therefore, it is relevant to perform these studies to dilucidate the expression changes involved in radioresistance.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3

et al. 2019

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Glioblastoma multiforme (GBM) is a poor prognosis type of tumour due to its resistance to chemo and radiotherapy. SOCS1 and SOCS3 have been associated with tumour progression and response to treatments in different kinds of cancers, including GBM. In this study, cell lines of IDH -wildtype GBM from primary cultures were obtained, and the role of SOCS1 and SOCS3 in the radiotherapy response was analysed. Fifty-two brain aspirates from GBM patients were processed, and six new cell lines of IDH -wildtype GBM were established. These new cell lines were characterized according to the WHO classification of CNS tumours. SOCS1 and SOCS3 expression levels were determined, at mRNA level by Q-PCR, at protein level by immunocytochemistry, and Western blot analysis. The results showed that SOCS1 and SOCS3 are overexpressed in GBM, as compared to a non-tumoral brain RNA pool. SOCS1 and SOCS3 expression were reduced by siRNA, and it was found that SOCS3 inhibition increases radioresistance in GBM cell lines, suggesting a key role of SOCS3 in radioresistant acquisition. In addition, radioresistant clonal populations obtained by selective pressure on these cell cultures also showed a significant decrease in SOCS3 expression, while SOCS1 remained unchanged. Furthermore, the induction of SOCS3 expression, under a heterologous promoter, in a radiotherapy resistant GBM cell line increased its radiosensitivity, supporting an important implication of SOCS3 in radiotherapy resistance acquisition. Finally, the treatment with TSA in the most radioresistant established cell line produced an increase in the effect of radiotherapy, that correlated with an increase in the expression of SOCS3 . These effects of TSA disappeared if the increase in the expression of SOCS3 prevented with an siRNA against SOCS3 . Thus, SOCS3 signal transduction pathway (JAK/STAT) could be useful to unmask new putative targets to improve radiotherapy response in GBM.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3

et al. 2019

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“…Poldip2 has been also described as playing a crucial role in Tau aggregation [26]. On another hand cellular functions, Poldip2 has been associated with diverse diseases such as cardiac pathologies [27], and breast and lung cancer diseases [28][29][30][31][32] and was shown to be involved in chemo-resistance [33]. By regulating mitochondrial lipoylation, Poldip2 allows cancer cells to adapt to hypoxic conditions in their new environment [34].…”

Section: Introductionmentioning

confidence: 99%

New insights in the molecular regulation of the NADPH oxidase 2 activity: Negative modulation by Poldip2

Bouraoui

Louzada

Aimeur

et al. 2023

Free Radical Biology and Medicine

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“…In a related set of functions, POLDIP2 favors cell division and proliferation through its effects on the mitotic spindle [ 24 ], as well as cell cycle activators and inhibitors [ 25 , 26 ]. These results may explain the association of POLDIP2 with various types of cancer [ 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Poldip2 knockout mice: Avoiding incorrect gene targeting

et al. 2021

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POLDIP2 is a multifunctional protein whose roles are only partially understood. Our laboratory previously reported physiological studies performed using a mouse gene trap model, which suffered from three limitations: perinatal lethality in homozygotes, constitutive Poldip2 inactivation and inadvertent downregulation of the adjacent Tmem199 gene. To overcome these limitations, we developed a new conditional floxed Poldip2 model. The first part of the present study shows that our initial floxed mice were affected by an unexpected mutation, which was not readily detected by Southern blotting and traditional PCR. It consisted of a 305 kb duplication around Poldip2 with retention of the wild type allele and could be traced back to the original targeted ES cell clone. We offer simple suggestions to rapidly detect similar accidents, which may affect genome editing using both traditional and CRISPR-based methods. In the second part of the present study, correctly targeted floxed Poldip2 mice were generated and used to produce a new constitutive knockout line by crossing with a Cre deleter. In contrast to the gene trap model, many homozygous knockout mice were viable, in spite of having no POLDIP2 expression. To further characterize the effects of Poldip2 ablation in the vasculature, RNA-seq and RT-qPCR experiments were performed in constitutive knockout arteries. Results show that POLDIP2 inactivation affects multiple cellular processes and provide new opportunities for future in-depth study of its functions.

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Gene expression changes associated with chemotherapy resistance in Ewing sarcoma cells

Cited by 10 publications

References 33 publications

Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3

Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3

New insights in the molecular regulation of the NADPH oxidase 2 activity: Negative modulation by Poldip2

Characterization of Poldip2 knockout mice: Avoiding incorrect gene targeting

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