miR-15b/16-2 Regulates Factors That Promote p53 Phosphorylation and Augments the DNA Damage Response following Radiation in the Lung

Rahman, Mohammad Aminur; Lovat, Francesca; Romano, Giulia; Calore, Federica; Acunzo, Mario; Bell, Erica H.; Nana‐Sinkam, Patrick

doi:10.1074/jbc.m114.573592

Cited by 53 publications

(28 citation statements)

References 33 publications

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“…24 In addition, miR15b has been established to be up-regulated following exposure to diverse stress-inducing agents, including ionizing radiation, etoposide, and hydrogen peroxide, which significantly influenced the cell cycle progression by targeting WIP1. 25 The demonstration that miR-33b-3p was dramatically downregulated when exposed to cisplatin and impacted on DDR by negative regulation of p21, further enlarged the knowledge and confirmed the effects of miRNAs on DNA damage response.…”

Section: Discussionmentioning

confidence: 80%

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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Section: Discussionmentioning

confidence: 80%

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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“…In addition, many of the controls in other studies did not undergo radiological investigations, such as computed tomography, whereas all the cases did in the present study. It is, therefore, possible that some of the changes in miRNA expression noted here are actually consequent to radiation exposure 33 . Finally, the recent discovery that miRNAs are present in the circulation has sparked interest in their use as potential biomarkers.…”

Section: Figurementioning

confidence: 97%

Tissue‐specific and plasma microRNA profiles could be promising biomarkers of histological classification and TNM stage in non‐small cell lung cancer

Huang

Liu

et al. 2016

Thoracic Cancer

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In a previous study, we determined that plasma miRNAs are potential biomarkers for cigarette smoking‐related lung fibrosis. Herein, we determine whether tissue‐specific and plasma miRNA profiles could be promising biomarkers for histological classification and TNM stage in non‐small cell lung cancer (NSCLC). Plasma miRNA profiling preoperatively and seven days postoperatively, and cancer and normal tissue miRNA profiling were performed in NSCLC patients and matched healthy controls. There was a > twofold change for all signature miRNAs between the NSCLC patients and controls, with P values of < 0.05. We found that tissue‐specific and plasma miR‐211‐3p, miR‐3679‐3p, and miR‐4787‐5p were promising biomarkers of different staging lung squamous cell carcinoma, and miR‐3613‐3p, miR‐3675‐3p, and miR‐5571‐5p were promising biomarkers of different staging lung adenocarcinoma. These results suggest that tissue‐specific and plasma miRNAs could be potential biomarkers of histological classification and TNM stage in NSCLC.

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“…miR-194-5p and miR-30a-5p have been shown to be associated with epithelial-mesenchymal transition, which is one of the hallmarks of more aggressive cancers [21,22]. Recent studies have demonstrated an important role for miR-15b-5p (and miR-16-5p that lies in the same genomic cluster), in regulating apoptosis, cell cycle and DNA repair pathways [23], and highlighted miR-15b-5p as a potential target for anti-cancer therapies [24]. Finally, miR-17-5p belongs to one of the most well-studied oncogenic miRNA clusters, miR-17/92, commonly found to be overexpressed in solid tumors including gastric and colorectal cancers [25].…”

Section: Discussionmentioning

confidence: 99%

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Chiam

Wang

Watson

et al. 2015

Journal of Gastrointestinal Surgery

121

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miR-15b/16-2 Regulates Factors That Promote p53 Phosphorylation and Augments the DNA Damage Response following Radiation in the Lung

Cited by 53 publications

References 33 publications

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

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

Tissue‐specific and plasma microRNA profiles could be promising biomarkers of histological classification and TNM stage in non‐small cell lung cancer

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

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miR-15b/16-2 Regulates Factors That Promote p53 Phosphorylation and Augments the DNA Damage Response following Radiation in the Lung

Cited by 53 publications

References 33 publications

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

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

Tissue‐specific and plasma microRNA profiles could be promising biomarkers of histological classification and TNM stage in non‐small cell lung cancer

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

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

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