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MiR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression.

ABSTRACT: Dysregulation of microRNA expression is involved in several pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of miR-363 in the progression and chemo-resistance of gastric cancer remain enigmatic. In this study, we validated that miR-363 expression was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identifies high levels of miR-363 expression as an independent predictor for postoperative recurrence and lower overall survival. Increased miR-363 expression promotes gastric cancer cell proliferation and chemo-resistance through directly targeting the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7). Clinically, our data reveal that overexpression of miR-363 correlates with the poor survival outcomes in patients with gastric cancer, and docetaxel + cisplatin + 5-FU (DCF) regimen response is impaired in patients with miR-363 overexpression. These data suggest that miR-363 may be a potential therapeutic target for gastric cancer and serve as a biomarker for predicting response to DCF regimen treatment.

SUBMITTER: Zhang PF

PROVIDER: S-EPMC5085228 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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miR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression.

Zhang Peng-Fei PF Sheng Lu-Lu LL Wang Ge G Tian Mi M Zhu Ling-Yin LY Zhang Rui R Zhang Jing J Zhu Jin-Shui JS

Oncotarget 20160601 23

Dysregulation of microRNA expression is involved in several pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of miR-363 in the progression and chemo-resistance of gastric cancer remain enigmatic. In this study, we validated that miR-363 expression was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identifies high levels of miR-363 expression as an independent predictor for ...[more]

PMID: 27167197

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Project description:OBJECTIVE:This study aimed to investigate the effect of circular RNA itchy E3 ubiquitin protein ligase on cell proliferation and apoptosis and to explore its target micro-RNAs in prostate cancer cells. METHODS:Circular RNA itchy E3 ubiquitin protein ligase expression in human prostate cancer cells and normal prostate epithelial cells was determined by real time-quantitative polymerase chain reaction assay. Circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids (circular RNA itchy E3 ubiquitin protein ligase(+) group and control overexpression plasmids group were transfected with PC-3 cells. Rescue experiment was performed by transfection of circular RNA itchy E3 ubiquitin protein ligase overexpression and micro-197 overexpression plasmids (circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids/micro RNA (+) group) into PC-3 cells. Cell Counting Kit-8 and annexin V/propidium iodide assays were conducted to evaluate cell proliferation and apoptosis, respectively. Western blot was performed to determine the expressions of apoptotic-related markers. RESULTS:Circular RNA itchy E3 ubiquitin protein ligase expression was decreased in DU 145, 22RV1, VCaP, and PC-3 cells compared to RWPE cells. In PC-3 cells, cell proliferation rate was reduced in circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids group compared to control overexpression plasmids group at 48 hours and 72 hours. Cell apoptosis rate was elevated in circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids group compared to control overexpression plasmids group at 48 hours, and Western blot showed the similar results. Micro RNA-197 but not micro RNA-31 or micro RNA-432 was the target micro-RNA of circular RNA itchy E3 ubiquitin protein ligase. In rescue experiments, cell proliferation rate was elevated, but apoptosis rate was reduced in circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids/micro RNA (+) group compared to circular RNA itchy E3 ubiquitin protein ligase overexpression plasmids group, indicating that circular RNA itchy E3 ubiquitin protein ligase upregulation inhibited cell proliferation but promoted apoptosis through downregulating micro RNA-197. CONCLUSION:Circular RNA itchy E3 ubiquitin protein ligase upregulation suppresses cell proliferation but promotes apoptosis through targeting micro RNA-197 in prostate cancer. Our study may provide a new insight for the treatment of prostate cancer.

Dataset Information

MiR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression.

Publications

miR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression.

Similar Datasets

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