miR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression
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Peng-Fei Zhang1,*, Lu-Lu Sheng2,*, Ge Wang1,*, Mi Tian2, Ling-Yin Zhu1, Rui Zhang1, Jing Zhang1, Jin-Shui Zhu1
1Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, P.R. China
2Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, P.R. China
*These authors have contributed equally to this work
Jin-Shui Zhu, email: firstname.lastname@example.org
Jing Zhang, email: email@example.com
Keywords: gastric cancer, microRNA-363, proliferation, chemo-resistance, FBW7
Received: December 17, 2015 Accepted: April 11, 2016 Published: May 4, 2016
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.
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