title: Chemotherapy-Induced miRNA-29c/Catenin-δ Signaling Suppresses Metastasis in Gastric Cancer.
abstract: Chemotherapy has improved the survival of patients with gastric cancer by unknown mechanisms. In this study, we showed that cisplatin and docetaxel used in gastric cancer treatment increase the expression of miRNA-29 (miR-29) family members and decrease the expression of their oncogenic targets, mediating a significant part of the efficacious benefits of these chemotherapeutic agents. In particular, patients with gastric cancer who experienced recurrences after chemotherapy tended to exhibit low levels of miR-29c expression in their tumors, suggesting that miR-29c activation may contribute to the chemotherapeutic efficacy. Enforced expression of miR-29s in gastric cancer cells inhibited cell invasion in vitro and in vivo by directly targeting catenin-δ (CTNND1). Drug treatment suppressed gastric cancer cell invasion by restoring miR-29c-mediated suppression of catenin-δ and RhoA signaling. In parallel, drug treatment also activated several tumor-suppressive miRNAs, thereby decreasing expression of their oncogenic effector targets. Overall, our findings defined a global mechanism for understanding the efficacious effects of cytotoxic chemotherapy in gastric cancer.
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China. Department of Thoracic Surgery, Center for Mini-invasive Thoracic Surgery, Shanxi Dayi Hospital, Shanxi Academy of Medical Sciences, Taiyuan, PR China.
authors: Yuxuan
authors: Y
authors: Wang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Changzheng
authors: C
authors: Liu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China. Department of Clinical Laboratory, Chengdu first People's Hospital, Chengdu, PR China.
authors: Min
authors: M
authors: Luo
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Zhengyi
authors: Z
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Jianan
authors: J
authors: Gong
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Jingjing
authors: J
authors: Li
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Lei
authors: L
authors: You
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Lei
authors: L
authors: Dong
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Rui
authors: R
authors: Su
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Haishuang
authors: H
authors: Lin
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Yanni
authors: Y
authors: Ma
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Fang
authors: F
authors: Wang
authors: Department of VIP, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors: Yi
authors: Y
authors: Wang
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Jie
authors: J
authors: Chen
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China.
authors: Junwu
authors: J
authors: Zhang
authors: Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, PR China. j-yu@ibms.pumc.edu.cn k-yan08@163.com swallow_jhy@163.com.
authors: Hongyan
authors: H
authors: Jia
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China. j-yu@ibms.pumc.edu.cn k-yan08@163.com swallow_jhy@163.com.
authors: Yan
authors: Y
authors: Kong
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, PR China. j-yu@ibms.pumc.edu.cn k-yan08@163.com swallow_jhy@163.com.
authors: Jia
authors: J
authors: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051177:Catenins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D000970:Antineoplastic Agents; D051177:Catenins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; D020741:rho GTP-Binding Proteins; D002945:Cisplatin; D000095002:Delta Catenin