title: Overexpression of Lin28 Decreases the Chemosensitivity of Gastric Cancer Cells to Oxaliplatin, Paclitaxel, Doxorubicin, and Fluorouracil in Part via microRNA-107.
abstract: Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28) increased their resistance to the chemo-drugs oxaliplatin (OXA), paclitaxel (PTX), doxorubicin (ADM), and fluorouracil (5-Fu) compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA) was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance.
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Rongyue
authors.initials: R
authors.lastname: Teng
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.|Zhejiang University, Hangzhou, Zhejiang province, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Zhejiang University, Hangzhou, Zhejiang province, People's Republic of China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Postgraduate Research Associate Yale School of Medicine, Department of Ob/Gyn & Reproductive Sciences, New Haven, Connecticut, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Seifer
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C000715187:Lin28A protein, human; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D011725:Pyridines; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C431073:oxiplatin; D004317:Doxorubicin; D017239:Paclitaxel; D005472:Fluorouracil