MiR-21 plays an Important Role in Radiation Induced Carcinogenesis in BALB/c Mice by Directly Targeting the Tumor Suppressor Gene Big-h3

Liu, Cong; Li, Bailong; Cheng, Ying; Lin, Jing; Hao, Jun; Zhang, Shuyu; Mitchel, R. E. J.; Sun, Ding; Jin, Ning; Zhao, Ling; Gao, Fu; Cai, Jianming

doi:10.7150/ijbs.7.347

Cited by 51 publications

(90 citation statements)

References 69 publications

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“…Detection is based on a click reaction [20], a copper catalyzed covalent reaction between an azide and an alkyne. Flow Cytometry Assay was performed by using CellQuest software (Becton Dickinson, Franklin Lakes, NJ, USA) as described previously [21,22]. For MTT assay, 500 cells per well were seeded in triplicate in a 96-well plate with complete growth medium.…”

Section: Methodsmentioning

confidence: 99%

miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

Zhang²,

Bai³

et al. 2014

Cell Physiol Biochem

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Background: Lung cancer is the leading cause of cancer-related mortality worldwide, with near 1.4 million deaths each year. NSCLC accounts for nearly 85% of all case of lung cancer. MiRNAs play important roles in regulation of gene expression at the post-transcriptional level. MiRNAs profiles may predict prognosis and disease recurrence in early-stage NSCLC. Our previous study proved that over-expression of ubiquitin specific peptidase 14 (USP14), a deubiquitinating enzyme, was associated with favorable prognosis in NSCLC patients and promoted tumor cells proliferation. Here, we tried to identify which miRNAs targeted USP14, and the roles of these miRNAs in NSCLC. Methods: MiR-4782-3p and its potential targeted genes were identified by bioinformatics algorithm. Dual luciferase reporter assay system was used to analyze the interaction between miR-4782-3p and targeted genes. Cell proliferation was assayed by MTT and BdU assay. MiRNAs and mRNA expression were assayed by qRT-PCR. USP14 protein level was assayed by Western blot. The role of miR-4782-3p in patients survival was revealed by Kaplan-Meier plot of overall survival. Results: Up-expression of miR-4782-3p in NSCLC cells decreased the USP14 expression. Down-expression of miR-4782-3p increased USP14 expression. In NSCLC specimen, Negative correlation between USP14 mRNA level and miR-4782-3p level was identified. Higher miR-4782-3p expression is associated with longer survival. USP14, ZEB2, XIAP overexpression reversed the inhibitory effect of miR-4782-3p. Conclusions: High expression of miR-4782-3p was associated with favorable prognosis in NSCLC patients. MiR-4782-3p inhibited cell proliferation in NSCLC by targeting USP14, ZEB2 and XIAP.

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Section: Methodsmentioning

confidence: 99%

miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

Zhang²,

Bai³

et al. 2014

Cell Physiol Biochem

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“…Ectopic expression of miR-21 increased radioresistance and inhibition of miR-21 by the PNA anti-miR-21 [25]. The radioresistance was caused by miR-21 directly targeting BIGH3, a transforming growth factor that is overexpressed in various types of cancer [25][26][27].…”

Section: Discussionmentioning

confidence: 98%

“…The radioresistance was caused by miR-21 directly targeting BIGH3, a transforming growth factor that is overexpressed in various types of cancer [25][26][27]. Wagner-Ecker et al reported that radiation increased miR-21 expression in human endothelial cells, suggesting an important role of miR-21 in improving the clonogenic survival of cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 inhibitor potentiates anti-tumor effect of radiation therapy in vitro and in vivo

Cho¹,

Kim²,

Lee³

et al. 2014

Tumor Microenvironment and Therapy

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MicroRNA-21 (miR-21) plays important roles in carcinogenesis and is highly expressed in diverse human cancers. We evaluated the potential of targeting miRNA-21 to overcome the radioresistance of human cancer cells having an activated EGFR2-associated signaling and also aimed to elucidate the mechanisms of radiosensitization, and the effect on epithelial- mesenchymal transition (EMT). Ectopic overexpression of miR-21 up-regulated EGFR/HER2-associated signaling and increased radioresistance of a panel of human cancer cells (U251, U87, and A549 cells). In contrast, a specific inhibitor of miR-21 attenuated this signaling and radiosensitized a panel of human cancer cells. Inhibition of miR-21 was associated with persistent γH2AX foci formation. Inhibition of miR-21 decreased the typical features of EMT, such as invasion and migration and vascular tube formation. Treatment with anti-miR-21 decreased tumor burden in nude mice bearing intracranial U251 xenografts compared to controls. Combined treatment of anti-miR-21 and radiation further decreased tumor burden compared to each treatment alone. In summary, miR-21 is an important onco-miR, which confers radioresistance and diverse features of EMT. Inhibition of miR-21 could be a potential strategy for improving the efficacy of radiation therapy via unique modulation of pro-survival signaling implicated in radiation response and EMT.

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“…Then these mice were routinely cared and observed daily. All mice were housed in a Specific Pathogen-Free (SPF) facility for all experiments [4,5,22,23,24]. All animal experiments were undertaken in accordance with the National Institute of Health "Guide for the Care and Use of Laboratory Animals" (NIH Publication No.…”

Section: Methodsmentioning

confidence: 99%

GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

Zhang

et al. 2013

Cell Physiol Biochem

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Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS), the ligands of Toll-like receptor 4(TLR4), could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β) promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6^-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6^-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.

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MiR-21 plays an Important Role in Radiation Induced Carcinogenesis in BALB/c Mice by Directly Targeting the Tumor Suppressor Gene Big-h3

Cited by 51 publications

References 69 publications

miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

MicroRNA-21 inhibitor potentiates anti-tumor effect of radiation therapy in vitro and in vivo

GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

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