title: MiR-181a suppresses autophagy and sensitizes gastric cancer cells to cisplatin.
abstract: A number of chemotherapy drugs can induce autophagy. This inducible autophagy is a pro-survival mechanism and contributes to the development of acquired drug resistance. Emerging evidence indicates that miRNA regulates autophagy via targeting autophagy related genes and is involved in drug resistance. We previously demonstrated that miR-181a plays an important role in gastric cancer. The present study aimed to explore the effect of miR-181a on autophagy regulation and cisplatin resistance. We revealed that miR-181a is a novel negative regulator of autophagy in cisplatin-resistant cells SGC7901/CDDP. Then we indicated that ATG5 was a potential target of miR-181a. Furthermore, overexpression of miR-181a significantly enhanced the sensitivity of SGC7901/CDDP cells to cisplatin in vitro and reduced the volumes of gastric tumor xenografts in nude mice. Our finding provides evidence that miR-181a functions as a primary autophagy-related modulator and reverses cisplatin-resistance in GC cells.
authors.affiliation: School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1 Panfu Road, Guangzhou 510180, PR China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1 Panfu Road, Guangzhou 510180, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1 Panfu Road, Guangzhou 510180, PR China. Electronic address: lysky1@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D002945:Cisplatin
keywords: ATG5; Autophagy; Drug resistance; Gastric cancer; miR-181a