Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

doi:10.1016/j.lssr.2016.04.002

Cited by 7 publications

(9 citation statements)

References 31 publications

(36 reference statements)

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“…DNA DSB Repair-To confirm miR-21-mediated radioresistance, we examined the survival sensitivity of miR-21 knock-in mice (generated in our lab (29)) and miR-21 knock-out mice (obtained from Dr. Olson's lab (30)) to IR. The miR-21 knockout mice or mouse embryo fibroblast (MEF) cells derived from the mice did not show a detectable miR-21 level.…”

Section: Mir-21-mediated Radioresistance Occurs Through Promotingmentioning

confidence: 99%

miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks

Wang

et al. 2017

Journal of Biological Chemistry

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miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR occurs through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase because GSK3B promotes degradation of both CDC25A and cyclin D1, but CDC25A and cyclin D1 have an opposite effect on HRR. A negative correlation of expression levels between miR-21 and GSK3β exists in a subset of human tumors. Our results not only elucidate miR-21-mediated radioresistance, but also provide potential new targets for improving radiotherapy.

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Section: Mir-21-mediated Radioresistance Occurs Through Promotingmentioning

confidence: 99%

miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks

Wang

et al. 2017

Journal of Biological Chemistry

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“…Unexpectedly, the young knock‐in mice did not show superiority during wound healing, which suggested that induced endogenous miR‐21 after wounding had already reached maximum saturation and was sufficient for proper wound repair. Similarly, miR‐21 knock‐in mice showed a decrease versus an increase in lung tumorigenesis after exposure to low‐ or high‐linear energy transfer radiation . Although the situation altered after aging, miR‐21 levels in both the basal homeostasis skin tissue and repairing granulations during wound healing were insufficient in aged mice (Figure ).…”

Section: Discussionmentioning

confidence: 97%

“…Similarly, miR-21 knock-in mice showed a decrease versus an increase in lung tumorigenesis after exposure to low-or high-linear energy transfer radiation. 26 Although the situation altered after aging, miR-21 levels in both the basal homeostasis skin tissue and repairing granulations during wound healing were insufficient in aged mice (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

“…All mice‐related experiments were approved by the Institutional Animal Care and Use Committee of Army Military Medical University (AMMU, Chongqing, China). miR‐21 knock‐in mice were obtained as a gift from the laboratory of Dr Ya Wang . In brief, the miR‐21 sequence under the CAG promoter was knocked in the X chromosome by homologus recombination.…”

Section: Methodsmentioning

confidence: 99%

“…miR-21 knock-in mice were obtained as a gift from the laboratory of Dr Ya Wang. 26,27 In brief, the miR-21 sequence under the CAG promoter was knocked in the X chromosome by homologus recombination. The knock-in mice were initially on a mixed C57BL/6 J and 129/SvEv background and were then backcrossed with C57BL/6 J mice to the F4 generation.…”

Section: Animalsmentioning

confidence: 99%

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