The miR-99 family regulates the DNA damage response through its target SNF2H

Mueller, Adam C.; Sun, Dandan; Dutta, Anindya

doi:10.1038/onc.2012.131

Cited by 124 publications

(120 citation statements)

References 46 publications

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“…Cells were used for experiments when they were around 60% to 70% confluent. Preferably, low passages (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were used. Irradiation assay Radiosensitivity assay.…”

Section: Methodsmentioning

confidence: 99%

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Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

Jong

Hoeve

Grénman

et al. 2015

Clinical Cancer Research

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Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance.Experimental Design: We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer.Results: miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer.Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors.

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Section: Methodsmentioning

confidence: 99%

“…miRs playing a role in radioresistance have been described, although experiments were done in cell line pairs and not in a larger panel of cell lines (18)(19)(20).…”

Section: Radioresistance Of Head and Neck Cancermentioning

confidence: 99%

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

Jong

Hoeve

Grénman

et al. 2015

Clinical Cancer Research

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“…14,15 Additionally, accumulating evidences have unraveled that miRNAs exerted critical roles in modulating the DNA damage response. [16][17][18][19] Thus, it's reasonable to speculate that DNA damage responsive miRNAs may exert a crucial role in modulating cisplatin sensitivity and drug resistance. In this study, we sought to screen differentially expressed miRNAs against cisplatin treatment, and further investigate into the effects of the identified DNA damage responsive miRNAs on cisplatin sensitivity, elucidating a novel molecular mechanism in the development of cisplatin resistance.…”

Section: Introductionmentioning

confidence: 99%

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

Huang

Chen

et al. 2016

Cell Cycle

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Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down-regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR33b-3p endowed the lung cancer cells with enhanced survival and decreased gH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers.

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“…miRNAs were selected to target more than one gene that is involved in different repair Genes involved in cell cycle checkpoint, nucleotide excision, base excision, double-strand break and mismatch repair pathways and the miRNAs targeting these genes are listed. These associations were either published previously [11,[47][48][49][50], or bioinformatics studies showed that these miRNAs target the mRNAs (http://www.targetscan.org/, http://www.microrna.org/microrna/home.do, http://mirdb.org/miRDB/) pathways to be able to have a general idea of the possible regulatory roles of miRNAs in DNA repair pathways. The expression of 20 miRNAs targeting these repair genes was analysed in 22 oocytes and 23 blastocysts, respectively.…”

Section: Resultsmentioning

confidence: 99%

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts

Tulay

Naja

Cascales-Roman

et al. 2015

J Assist Reprod Genet

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Purpose The aim of the study is to investigate the regulation of DNA repair genes by microRNAs (miRNAs). miRNAs are short non-coding RNAs that regulate transcriptional and post-transcriptional gene silencing. Several miRNAs that are expressed during preimplantation embryo development have been shown or are predicted to target genes that regulate cell cycle checkpoints and DNA repair in response to DNA damage. Methods This study compares the expression level of 20 miRNAs and 9 target transcripts involved in DNA repair. The statistical significance of differential miRNA expression between oocytes and blastocysts was determined by t test analysis using the GraphPad Prism v6 software. The possible regulatory roles of miRNAs on their target messenger RNAs (mRNAs) were analysed using a Pearson correlation test. Results This study shows for the first time that several miRNAs are expressed in human oocytes and blastocysts that target key genes involved in DNA repair and cell cycle checkpoints. Blastocysts exhibited statistically significant lower expression levels for the majority of miRNAs compared to oocytes (p<0.05). Correlation analyses showed that there was both inverse and direct association between miRNAs and their target mRNAs. Conclusions miRNAs target many mRNAs including ones involved in DNA repair mechanisms. This study suggests that miRNAs and their target mRNAs involved in DNA repair are expressed in preimplantation embryos. Similar to the miRNAs expressed in adult tissues, these miRNAs seem to have regulatory roles on their target DNA repair mRNAs during preimplantation embryo development.

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The miR-99 family regulates the DNA damage response through its target SNF2H

Cited by 124 publications

References 46 publications

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts

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The miR-99 family regulates the DNA damage response through its target SNF2H

Cited by 124 publications

References 46 publications

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts

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DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1