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DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung cancer cell lines)

ABSTRACT: The DNA damage response (DDR) is a cellular process that protects the genetic information against DNA damage and inhibits malignant transformation. Tumor cells are characterized by an aberrant DDR, which is exploited by genotoxic chemotherapy. However, cancer cells are able to develop drug resistance, for example by modulation of the DDR. Although the regulation of the DDR has been extensively studied, not much is known about the role of microRNAs (miRNAs). Here, we describe an approach to specifically identify DDR miRNAs in human primary epithelial cells that also play a role in tumorigenesis and response to cancer therapy in corresponding cancer cells. The miRNA expression profile was determined of 12 lung cancer cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Wouters Maikel

PROVIDER: S-ECPF-GEOD-47524 | biostudies-other |

REPOSITORIES: biostudies-other

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DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung tumors)

Project description:The DNA damage response (DDR) is a cellular process that protects the genetic information against DNA damage and inhibits malignant transformation. Tumor cells are characterized by an aberrant DDR, which is exploited by genotoxic chemotherapy. However, cancer cells are able to develop drug resistance, for example by modulation of the DDR. Although the regulation of the DDR has been extensively studied, not much is known about the role of microRNAs (miRNAs). Here, we describe an approach to specifically identify DDR miRNAs in human primary epithelial cells that also play a role in tumorigenesis and response to cancer therapy in corresponding cancer cells. The miRNA expression profile was determined of 18 non-small cell lung tumors and 16 normal lung samples.

| S-ECPF-GEOD-47525 | biostudies-other

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung cancer cell lines)

2013-05-31 | E-GEOD-47524 | biostudies-arrayexpress

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung cancer cell lines)

2013-05-31 | GSE47524 | GEO

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung tumors)

2013-05-31 | E-GEOD-47525 | biostudies-arrayexpress

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-05-31 | E-GEOD-47526 | biostudies-arrayexpress

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (lung tumors)

2013-05-31 | GSE47525 | GEO

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-05-31 | GSE47526 | GEO

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (HMEpC & HSAEpC)

Project description:The DNA damage response (DDR) is a cellular process that protects the genetic information against DNA damage and inhibits malignant transformation. Tumor cells are characterized by an aberrant DDR, which is exploited by genotoxic chemotherapy. However, cancer cells are able to develop drug resistance, for example by modulation of the DDR. Although the regulation of the DDR has been extensively studied, not much is known about the role of microRNAs (miRNAs). We used an approach to specifically identify DDR miRNAs in human primary epithelial cells that also play a role in tumorigenesis and response to cancer therapy in corresponding cancer cells. The miRNA expression profile was determined in 132 samples: 2 primary epithelial cell types, 1 untreated sample, 4 genotoxic treated samples, 3 timepoints, 4 replicates each and 6 zero timepoints for each cell type

2013-05-31 | E-GEOD-47523 | biostudies-arrayexpress

DNA damage responsive microRNAs misexpressed in human cancer regulate chemotherapy sensitivity (HMEpC & HSAEpC)

Project description:The DNA damage response (DDR) is a cellular process that protects the genetic information against DNA damage and inhibits malignant transformation. Tumor cells are characterized by an aberrant DDR, which is exploited by genotoxic chemotherapy. However, cancer cells are able to develop drug resistance, for example by modulation of the DDR. Although the regulation of the DDR has been extensively studied, not much is known about the role of microRNAs (miRNAs). We used an approach to specifically identify DDR miRNAs in human primary epithelial cells that also play a role in tumorigenesis and response to cancer therapy in corresponding cancer cells.

2013-05-31 | GSE47523 | GEO

DNA damage responsive microRNAs misexpressed in human cancer modulate therapy sensitivity.

Project description:The DNA damage response (DDR) is activated upon DNA damage and prevents accumulation of mutations and chromosomal rearrangements, both driving carcinogenesis. Tumor cells often have defects in the DDR, which in combination with continuous cell proliferation are exploited by genotoxic cancer therapies. Most cancers, overcome initial sensitivity and develop drug resistance, e.g. by modulation of the DDR. Not much is known, however, about DNA damage responsive microRNAs in cancer therapy resistance. Therefore, we mapped temporal microRNA expression changes in primary breast epithelial cells upon low and high dose exposure to the DNA damaging agents ionizing radiation and cisplatin. A third of all DDR microRNAs commonly regulated across all treatments was also misexpressed in breast cancer, indicating a DDR defect. We repeated this approach in primary lung epithelial cells and non-small cell lung cancer samples and found that more than 40% of all DDR microRNAs was deregulated in non-small cell lung cancer. Strikingly, the microRNA response upon genotoxic stress in primary breast and lung epithelial cells was markedly different, although the biological outcome of DNA damage signaling (cell death/senescence or survival) was similar. Several DDR microRNAs deregulated in cancer modulated sensitivity to anti-cancer agents. In addition we were able to distinguish between microRNAs that induced resistance by potentially inducing quiescence (miR-296-5p and miR-382) or enhancing DNA repair or increased DNA damage tolerance (miR-21). In conclusion, we provide evidence that DNA damage responsive microRNAs are frequently misexpressed in human cancer and can modulate chemotherapy sensitivity.

| S-EPMC4685152 | biostudies-literature

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