title: MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN.
abstract: Multidrug resistance (MDR) is the major cause of failure of gastric cancer chemotherapy. Members of the miR-17-92 cluster, including miR-19a/b, are considered oncomiRs and influence multiple aspects of the malignant phenotype of gastric cancer. However, the role of miR-19a/b in MDR in gastric cancer and its underlying mechanism remain unclear. In this study, we found that miR-19a/b were upregulated in MDR cell lines. Our results also showed that miR-19a/b upregulation decreased the sensitivity of gastric cancer cells to anticancer drugs. We further confirmed that miR-19a/b accelerated the ADR efflux of gastric cancer cells by increasing the levels of mdr1 and P-gp and that miR-19a/b suppressed drug-induced apoptosis by regulating Bcl-2 and Bax. Finally, we verified that PTEN, an inhibitor of AKT phosphorylation, is the functional target of miR-19a/b. Overall, these findings demonstrated that miR-19a/b promote MDR in gastric cancer cells by targeting PTEN.
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000473:pathology*; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; C549214:MIRN19A microRNA, human; D035683:MicroRNAs